Compositions and methods for targeted delivery of chemicals and biomolecules to plants and fungi

Abstract

The present invention provides methods and compositions for targeted delivery of chemical or biomolecular cargo and / or nanoparticles to plant phloem or fungi.

Description

[0001] Related Applications

[0002] This application claims the benefit of priority to U.S. Provisional Application Serial No. 63 / 316,902, filed on March 4, 2022, which is incorporated herein by reference.

[0003] Government funding

[0004] This invention was made with government support under Grant No. 1911763 awarded by the National Science Foundation. The government has certain rights in this invention. Background Art

[0005] Rapid population growth has led to an increasing global demand for agricultural productivity, which requires significant increases in food production. Agricultural practices have created some of the most significant pressures on the Earth's natural resources, leading to deforestation, groundwater contamination, and increased greenhouse gas emissions. The runoff of agricultural chemicals (such as pesticides and fertilizers) from farmland is one of the most negative impacts on the environment and human health. Pesticides are the main type of agricultural chemicals that accumulate in the environment; progressive biomagnification can transfer pesticides into the food chain. While the use of pesticides has increased the yield and quality of crops, excessive use of pesticides and herbicides has led to the development of resistance in agricultural pests (e.g., pathogens), affected air quality, and contaminated water and soil. This is particularly worrying because it is estimated that of the 5.6 billion pounds of pesticides applied worldwide, less than 0.1% achieve their intended biological targets.

[0006] As a result, the efficiency of delivery of agrochemicals to the desired site of action is relatively low, resulting in suboptimal efficacy and undesirable environmental side effects. New methods and compositions are needed for improving the delivery of agrochemicals to plants and fungi. Summary of the invention

[0007] Certain embodiments of the present invention provide a conjugate comprising a sucrose transporter (SUT) targeting agent linked to a cargo selected from a pesticide, a herbicide, or a fertilizer.

[0008] Certain embodiments provide a conjugate comprising a sucrose transporter (SUT) targeting agent linked to a cargo (e.g., directly or indirectly), wherein the conjugate is capable of being delivered to a plant or fungus, and wherein the cargo is an agent capable of producing a desired effect in the plant or fungus upon delivery of the conjugate to the plant or fungus.

[0009] In certain embodiments, the conjugate further comprises nanoparticles and / or molecular baskets, wherein the nanoparticles are selected from the group consisting of quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, metal or metal oxide nanoparticles, and nanoparticles based on micronutrients or macronutrients. In certain embodiments, the nanoparticles are attached to one or more SUT targeting agents. In certain embodiments, the cargo is associated with the nanoparticles or with the molecular basket. In certain embodiments, the cargo is associated with the nanoparticles. In certain embodiments, the cargo is associated with the molecular basket. In certain embodiments, the molecular basket comprises beta cyclodextrin or gamma cyclodextrin.

[0010] Certain embodiments provide a conjugate comprising a sucrose transporter (SUT) targeting agent attached to a nanoparticle (e.g., comprising one or more SUT targeting agents attached to a nanoparticle), wherein the conjugate is capable of being delivered to a plant or fungus, and the nanoparticle is selected from the group consisting of: quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, metal or metal oxide nanoparticles, and micro- or macronutrient-based nanoparticles.

[0011] Certain embodiments of the present invention provide a conjugate comprising a glucose transporter (GUT) targeting agent linked to a cargo selected from a pesticide, a herbicide, or a fertilizer.

[0012] Certain embodiments provide a conjugate comprising a glucose transporter (GUT) targeting agent linked to a cargo (e.g., directly or indirectly), wherein the conjugate is capable of being delivered to a fungus, and wherein the cargo is an agent capable of producing a desired effect in the fungus upon delivery of the conjugate to the fungus.

[0013] In certain embodiments, the conjugate further comprises nanoparticles and / or molecular baskets, wherein the nanoparticles are selected from the group consisting of quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, and metal or metal oxide nanoparticles. In certain embodiments, the nanoparticles are attached to one or more GUT targeting agents. In certain embodiments, the cargo is associated with the nanoparticles or with the molecular basket. In certain embodiments, the cargo is associated with the nanoparticles. In certain embodiments, the cargo is associated with the molecular basket. In certain embodiments, the molecular basket comprises beta cyclodextrin or gamma cyclodextrin.

[0014] Certain embodiments provide a conjugate comprising a glucose transporter (GUT) targeting agent attached to a nanoparticle (e.g., comprising one or more GUT targeting agents attached to a nanoparticle), wherein the conjugate is capable of being delivered to a fungus, and the nanoparticle is selected from the group consisting of: quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, and metal or metal oxide nanoparticles.

[0015] Certain embodiments of the present invention provide a conjugate comprising a cargo and a conjugate of formula I as described herein, and optionally one or more molecular baskets, wherein the cargo is associated with a nanoparticle and / or a molecular basket, and wherein the cargo is selected from a pesticide, a herbicide, or a fertilizer. Certain embodiments of the present invention provide a conjugate comprising a conjugate of formula II as described herein, wherein the cargo is selected from a pesticide, a herbicide, or a fertilizer. Certain embodiments of the present invention provide a conjugate comprising a cargo and a conjugate of formula III as described herein, and optionally nanoparticles, wherein the cargo is associated with a molecular basket and / or a nanoparticle, and wherein the cargo is selected from a pesticide, a herbicide, or a fertilizer. In certain embodiments, the targeting agent is a SUT targeting agent (e.g., a disaccharide, such as sucrose). In certain embodiments, the targeting agent is a GUT targeting agent (e.g., a monosaccharide, such as glucose).

[0016] Certain embodiments provide a conjugate as described herein.

[0017] Certain embodiments provide a method of introducing a conjugate into a plant or fungus (eg, a plant or fungus expressing a sucrose transporter (SUT) protein), the method comprising contacting the plant or fungus with a conjugate as described herein.

[0018] Certain embodiments provide a method of treating a fungal infection in a plant or introducing a conjugate into a fungus, the method comprising contacting the plant and / or fungus (e.g., a plant and / or fungus expressing a glucose transporter (GUT) protein) with a conjugate as described herein.

[0019] Certain embodiments provide a method for delivering a conjugate to a plant or fungus, comprising contacting the plant or fungus with a conjugate comprising nanoparticles and / or molecular baskets linked to a sucrose transporter (SUT) targeting agent (e.g., linked to one or more SUT targeting agents), wherein the nanoparticles are selected from the group consisting of quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, metal or metal oxide nanoparticles, and micro- or macronutrient-based nanoparticles.

[0020] Certain embodiments provide a method for introducing a conjugate into a fungus, comprising contacting the fungus with a conjugate comprising nanoparticles and / or molecular baskets linked to a glucose transporter (GUT) targeting agent (e.g., linked to one or more GUT targeting agents), wherein the nanoparticles are selected from the group consisting of quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, and metal or metal oxide nanoparticles.

[0021] Certain embodiments provide a method for introducing a conjugate into a fungus, comprising contacting the fungus with a conjugate comprising nanoparticles and / or molecular baskets linked to a glucose transporter (GUT) targeting agent, wherein the nanoparticles are selected from the group consisting of quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, and metal or metal oxide nanoparticles, and wherein the conjugate is contacted with the fungus during germination.

[0022] Certain embodiments provide a method for introducing a conjugate into a fungus, comprising contacting the fungus with a conjugate comprising nanoparticles and / or molecular baskets linked to a glucose transporter (GUT) targeting agent, wherein the nanoparticles are selected from the group consisting of quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, and metal or metal oxide nanoparticles, and wherein the conjugate is contacted with the fungus after germination.

[0023] Certain embodiments provide a method for introducing a conjugate into a fungus, comprising contacting the fungus with a conjugate comprising nanoparticles and / or molecular baskets linked to a glucose transporter (GUT) targeting agent, wherein the nanoparticles are selected from the group consisting of quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, and metal or metal oxide nanoparticles, and wherein the conjugate is contacted with the fungus during proliferation.

[0024] Certain embodiments provide a method for introducing a conjugate into a fungus, comprising contacting the fungus with a conjugate comprising nanoparticles and / or molecular baskets linked to a glucose transporter (GUT) targeting agent, wherein the nanoparticles are selected from the group consisting of quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, and metal or metal oxide nanoparticles, and wherein the conjugate is contacted with the fungus while the fungus is forming hyphae.

[0025] Certain embodiments provide a method for introducing a conjugate into a fungus, comprising contacting the fungus with a conjugate comprising nanoparticles and / or molecular baskets linked to a glucose transporter (GUT) targeting agent, wherein the nanoparticles are selected from the group consisting of quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, and metal or metal oxide nanoparticles, and wherein the conjugate is contacted with the fungus during sporulation.

[0026] Certain embodiments provide a method comprising detecting a conjugate as described herein in a plant or fungus.

[0027] Certain embodiments provide a method as described herein.

[0028] The present invention also provides processes and intermediates disclosed herein that can be used to prepare the conjugates described herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1A-1B Figure 1a) Targeted delivery of nanomaterials to the phloem via plant biorecognition. Sucrose-coated quantum dots (sucQD) and sucrose-β-cyclodextrin-coated carbon dots topically applied to the leaf surface are guided through the leaf tissue into the phloem via biorecognition by sucrose transporters (SUTs) located in the phloem vessels. Figure 1b) The upper schematic shows sucQDs; the lower schematic shows sucrose-coated carbon dots (CDs) coated with β-cyclodextrin.

[0030] Figure 2A-2G. Characterization of sucrose-coated QDs (sucQDs) and sucrose-coated β-cyclodextrin CDs (suc-β-CDs). Figure 2a), TEM images of sucQDs with an average size of 4.1 nm and suc-β-CDs with an average size of 9.1 nm. Figure 2b), Hydrodynamic sizes of QDs, sucQDs, core CDs, and suc-β-CDs. Figure 2c), QDs, sucQDs, CDs, and suc-β-CDs all have negative zeta potentials (TES buffer, pH 7.0). n=6-8. Figure 2d), Absorption spectra of QDs, sucQDs, CDs, and suc-β-CDs. Compared to QDs, sucQDs show a slight increase in absorbance in the UV region due to the presence of sucrose coating. The absorption shape of suc-β-CD becomes broadened after functionalization with β-cyclodextrin and sucrose. Figure 2e), the fluorescence emission spectra of QD, sucQD, CD and Suc-β-CD do not overlap with the leaf background fluorescence. Figure 2f-2g) FT-IR spectra of sucQD and Suc-β-CD, which indicate that the surface is functionalized with sucrose or β-cyclodextrin.

[0031] Figure 3A-3C. Confocal microscopy imaging of nanomaterial entry into phloem cells. Figure 3a) In vivo confocal fluorescence microscopy images near the foliar application area of ​​sucQD. sucQD (light gray) is localized in the vascular system of wheat leaves between mesophyll cells containing chloroplasts (dark gray). Scale bar = 100 μm. Figure 3b) Representative images showing the high co-localization of sucQD with CF fluorescent dye labeling phloem cells (dark gray). Scale bar = 30 μm. Figure 3c) In vivo confocal fluorescence microscopy images of sucrose-coated CDs in the foliar application area. After coating with sucrose, CDs can be efficiently localized in the vascular system of wheat leaves, while uncoated CDs form spherical structures throughout the leaf mesophyll. Scale bar = 100 μm.

[0032] FIG4A-FIG4E. Rapid uptake and translocation of sucQDs in the phloem are mediated by plant biorecognition. FIG4a) Live imaging of QDs in the phloem of wheat leaves in planta in a custom-built inverted epifluorescence microscope. Wheat leaves from intact living plants were mounted on the microscope stage, and FIG4b) a tracking region 10 mm from the loading region was excited to image QD translocation in the phloem. FIG4c) Fluorescence intensity changes in the tracking region indicate rapid loading and translocation of sucQDs in the phloem. The sucQD fluorescence intensity changes were significantly higher than those of unmodified QDs and glucose-coated QDs (gluQDs). FIG4d) Epifluorescence images of the vascular system of wheat leaves after exposure to sucQDs (40 min) indicate potential pathways for sucQD phloem loading and leaf uptake through stomata. FIG4e) Differences in sucQD translocation in the phloem at 4°C and 25°C indicate an energy-dependent mechanism for nanoparticle loading and translocation into the phloem. n=4. Scale bar = 50 μm

[0033] Figure 5 Delivery of QDs from leaves to other plant organs via the phloem. Schematic representation of the topical application of QDs and sucQDs to leaf regions, including exposed and traced leaf regions. Phloem vessels facilitate sap transport to stems and roots.

[0034] Figure 6A-6B Figure 6a) Synthesis of sucrose-coated QDs from carboxylated QDs. Figure 6b) Sucrose, β-cyclodextrin-coated CDs.

[0035] Figure 7 Compared with QDs, the FT-IR spectrum of sucQDs indicated the presence of sucrose and APBA.

[0036] Figure 8.sucQD and QD had no effect on photosynthesis in wheat leaves at different levels of photosynthetically active radiation (PAR). Plant leaves exposed to sucQD and QD (200 nM) or TES buffer without nanoparticles (control) for 30 min had similar rates of carbon dioxide assimilation.

[0037] Fig. 9 .Fluorescence emission spectra of CF, sucQDs and leaves under 405 nm excitation and comparison with the emission range of other components.

[0038] Figure 10A-10B. Figure 10a) Confocal fluorescence microscopy images of wheat leaves with CF-labeled phloem and sucQD-exposed leaves. Figure 10b) 3D renderings of CF- and sucQD-treated leaves created in FIJI. Scale bar = 100 μm.

[0039] Fig.11 .Epifluorescence microscopy images of wheat leaves exposed to sucQDs, QDs, and gluQDs for 40 min. Scale bar = 100 μm.

[0040] Fig.12 .Composition of synthetic phloem sap.

[0041] Fig.13 .Hydrodynamic size and zeta potential of QDs, sucQDs, and gluQDs dispersed in TES buffer (pH 7.4).

[0042] Fig.14A- Figure 14I. Design and characterization of nanocarriers for targeted delivery of fungicide active ingredients. Figure 14a) Nanocarriers target active ingredients to fungi in plants by recognizing glucose transporters (GUTs) on fungal cell membranes. Figure 14b) The nanocarriers in this example, i.e., β-cyclodextrin or γ-cyclodextrin / glucose coated Gd-doped carbon dots (glu-β-GdCD), consist of three components: a biorecognition moiety (glucose), fluorescent nanoparticles (carbon dots), and a molecular basket for loading fungicides. Glucose-coated nanocarriers have a higher binding affinity for fungal cells, which is mediated by biorecognition between glucose and GUT membrane proteins on the surface of the nanoparticles. Figure 14c) UV-visible absorbance of targeted β-GdCD and γ-GdCD. Figure 14d) The fluorescence emission (e.g., 355 nm) of glu-β-GdCD and glu-γ-GdCD does not overlap with leaf autofluorescence. Figure 14e) FTIR spectrum of glu-β-GdCD compared to core GdCD. Figure 14f) AFM image of core GdCD and height profiles of Figure 14g) core GdCD, Figure 14h) β-GdCD and Figure 14i) γ-GdCD. We observed an increase in nanoparticle thickness after functionalization with molecular baskets.

[0043] Figure 15A-Figure 15D. Enhanced delivery of nanocarriers functionalized with glucose to fungi in vitro. Figure 15a) In vitro assays were performed on incubation of GFP Botrytis hyphae with nanocarriers, followed by washing with DI water and confocal microscopy imaging. Figure 15b) Representative confocal images of GFP Botrytis exposed to nanocarriers show enhanced uptake of glucose-coated glu-β-GdCD by fungi. Figure 15c) Colocalization analysis of GdCD and GFP Botrytis fluorescence signals showed that the percentage of GFP colocalized with targeted glu-β-GdCD was significantly higher than that of control counterparts without glucose coating (single-factor ANOVA and post hoc test, n=3-4, **, p<0.01). Figure 15d) Orthogonal views of z-stacked confocal images of GFP Botrytis were performed using line cross-sections and show the overlap of fluorescence peaks corresponding to GFP and GdCD. Scale bar 100 μm.

[0044] Fig.16A- Figure 16C. Targeted delivery of nanocarriers coated with glucose to fungi in infected leaves. Figure 16a) In vivo confocal images of leaves infected with GFP Botrytis, showing a higher degree of co-localization of nanocarriers coated with glucose (glu-β-GdCD and glu-γ-GdCD) with GFP fluorescence compared to non-targeted nanocarriers (β-GdCD). Figure 16b) The co-localization rate of glu-β-GdCD with GFP is enhanced compared to β-GdCD. (t-test, n=3). Lowercase letters represent significance of P<0.05. Figure 16c) Orthogonal views from Z-stack confocal images showing co-localization of glu-β-GdCD within GFP Botrytis. Scale bar, 100 μm.

[0045] Fig.17A - Figure 17F. In vitro delivery of fluorescent chemical cargo to fungi mediated by nanocarriers. Figure 17a) Chemical structures of molecular baskets (cyclodextrin) and fluorescent chemical cargo (Rhodamine 6G, R6G) Figure 17b) Fluorescence spectra of R6G in the presence of different concentrations of β-cyclodextrin (0-10 mM, TES buffer, pH 7.4) Figure 17c) Dose-dependent fluorescence response of R6G interacting with β-cyclodextrin and γ-cyclodextrin. Figure 17d) Confocal images of leaves infected with GFP Botrytis, which show that compared with non-targeted nanocarriers (β-GdCD and γ-GdCD), the nanocarriers coated with glucose (glu-β-GdCD and glu-γ-GdCD) have a higher degree of co-localization with GFP fluorescence. Figure 17e) The co-localization rate of glu-γ-GdCD with GFP is enhanced compared with γ-GdCD. (t-test, n=3). Fig. 17f) Orthogonal views from z-stack confocal images co-localizing R6G with glu-γ-GdCD in GFP Botrytis. Scale bar, 100 μm.

[0046] FIG. 18A-C. Targeted delivery of fluorescent chemical cargo to fungi in infected leaves mediated by nanocarriers FIG. 18a) Confocal images of GFP Botrytis infected leaves showing a higher degree of colocalization of R6G delivered by glu-γ-GdCD with GFP fluorescence compared to non-targeted γ-GdCD. FIG. 18b) Colocalization ratio of R6G delivered by glu-γ-GdCD with GFP compared to γ-GdCD. (One-way ANOVA post hoc test, n=3, *, p<0.05. FIG. 18c) Orthogonal views from Z-stacks of confocal images showing colocalization of glu-β-GdCD within GFP Botrytis. Scale bar, 100 μm.

[0047] Fig.19Synthesis of sucrose or glucose coated nanocarriers (suc-β-GdCD, glu-β-GdCD) for targeted delivery of cargo. Detailed methods are provided in Example 3.

[0048] Fig. 20 Confocal images of nanocarriers in wild-type fungi (Botrytis spp.) in vitro. The confocal images showed that the fluorescence intensity of Botrytis spp. treated with Glu-b-GdCD was the highest.

[0049] Fig.21 . Confocal images of GFP Botrytis cinerea incubated with nanocarriers in vitro.

[0050] Fig. 22 .Targeted delivery of nanocarriers to fungal structures.

[0051] Fig.23 . In vivo Botrytis cinerea inoculation in detached leaf assays.

[0052] Fig.24 GFP Botrytis infected leaves were treated with 0.1% Silwet and sucrose coated carbon dot NPs for 3 hours (40X).

[0053] Fig.25 GFP Botrytis infected leaves were treated with 0.1% Silwet and sucrose coated carbon dot NPs for 3 hours (40X). DETAILED DESCRIPTION

[0054] Described herein are methods and compositions for improving the delivery of exogenous materials to plants or fungi. For example, it has been shown herein to enhance delivery to the phloem, stems and / or roots of plants by, for example, targeting the sucrose transporter (SUT) of the plant.

[0055] Sucrose transporters (SUT) are expressed in both plants and fungi. For example, plant sucrose transporters (SUT) expressed in the inner wall cells of phloem vessels load sucrose synthesized by leaves into phloem veins for transport to stems and roots. As described herein, by targeted biological recognition of sucrose transporters (SUT), the delivery efficiency and mass transport of exogenously introduced materials after foliar application can be increased (see, e.g., Example 1). Therefore, by the promotion of this SUT-mediated targeted delivery method, a higher proportion of exogenously introduced materials can enter the phloem vascular system and reach the desired destination compartment of the plant, thereby effectively improving the bioavailability of exogenously introduced materials. Fungi also express SUT, and exogenously introduced materials (such as the conjugates described herein) can be delivered throughout the fungi using the targeted biological recognition of these SUT proteins.

[0056] In addition, glucose transporter (GUT) is expressed in fungi. For example, the glucose transporter (GUT) expressed by fungal cells can promote the transport of monosaccharides (such as glucose), which can be used as a carbon source to provide energy or maintain the growth of fungal cells. As described herein, by targeted biological recognition of glucose transporter (GUT) expressed by fungal cells, the delivery efficiency of exogenous materials to fungal cells can be enhanced (see, e.g., Example 2).

[0057] Composition

[0058] Certain embodiments of the invention provide 1) a conjugate comprising a sucrose transporter (SUT) targeting agent linked to a cargo, wherein the conjugate is capable of being delivered to a plant or fungus; or 2) a conjugate comprising a glucose transporter (GUT) targeting agent, wherein the conjugate is capable of being delivered to a fungus; and wherein the cargo is an agent capable of producing a desired effect in the plant or fungus upon delivery of the conjugate to the plant or fungus.

[0059] Certain embodiments of the present invention provide a conjugate comprising a sucrose transporter (SUT) targeting agent linked to a cargo, wherein the conjugate is capable of being delivered to a plant or fungus (e.g., delivered to a desired site within the plant, such as the phloem, via the SUT protein), and wherein the cargo is an agent capable of producing a desired effect in the plant or fungus upon delivery of the conjugate to the plant or fungus.

[0060] Certain embodiments of the present invention provide a conjugate comprising a glucose transporter (GUT) targeting agent linked to a cargo, wherein the conjugate is capable of being delivered to a fungus, and wherein the cargo is an agent capable of producing a desired effect (e.g., an inhibitory effect) in the fungus upon delivery of the conjugate to the fungus.

[0061] Certain embodiments of the present invention provide a conjugate comprising a sucrose transporter (SUT) targeting agent or a glucose transporter (GUT) targeting agent linked to a cargo, which is a pesticide, a herbicide, or a fertilizer.

[0062] In certain embodiments, a conjugate as described herein comprises a mixture of SUT and GUT targeting agents.

[0063] As used herein, the term "conjugate" includes two or more elements that are reversibly or irreversibly combined, linked or joined.

[0064] In certain embodiments, the conjugate further comprises nanoparticles and / or cyclodextrin molecular baskets. For example, in certain embodiments, nanoparticles (NPs) and / or molecular baskets can be used as delivery vehicles or carriers for cargo. For example, cargo carried or captured by such a delivery system may be released in plants or fungi. Specifically, when connected to a SUT targeting agent, a higher proportion of such delivery vehicles (e.g., NPs and / or molecular baskets) can be introduced into plants (e.g., leaf surfaces) or fungi and reach the target site of action (e.g., phloem vessels and / or roots), and thus improve cargo exposure at the site of action. In certain embodiments, when connected to a GUT targeting agent, a higher proportion of such delivery vehicles (e.g., NPs and / or molecular baskets) can be introduced into fungi compared to a control delivery vehicle without a GUT targeting agent.

[0065] Thus, in certain embodiments, the cargo is associated with the nanoparticle and / or the cyclodextrin molecular basket (ie, the cargo is linked to the SUT or GUT targeting agent via its association with the nanoparticle and / or the cyclodextrin molecular basket).

[0066] In certain embodiments, the cargo is associated with the nanoparticle. For example, in certain embodiments, the cargo is conjugated to the surface of the nanoparticle or loaded into the nanoparticle (e.g., cargo loaded into porous silica nanoparticles). Thus, the cargo can be indirectly connected to the SUT or GUT targeting agent via nanoparticles functionalized with the SUT or GUT targeting agent.

[0067] As used herein, the term "functionalized" or "functionalized" refers to a compound or material (e.g., a nanoparticle) that has been modified to impart additional functionality (e.g., a targeting function or a function with enhanced cargo loading capacity) to the compound or material. For example, a SUT or GUT targeting agent and / or a molecular basket can be functionalized by attaching it to the surface of the nanoparticle.

[0068] In certain embodiments, the conjugate comprises a nanoparticle (NP) linked to one or more sucrose transporter (SUT) targeting agents.

[0069] In certain embodiments, the conjugate comprises a nanoparticle (NP) linked to one or more glucose transporter (GUT) targeting agents.

[0070] In some embodiments, the cargo is associated with a cyclodextrin molecular basket. For example, in some embodiments, the cargo is loaded in a cyclodextrin molecular basket. In some embodiments, the cargo forms an inclusion complex with the cyclodextrin. Therefore, the cargo can be indirectly connected to the SUT or GUT targeting agent via a cyclodextrin molecular basket (e.g., a cyclodextrin molecular sieve functionalized with a SUT or GUT targeting agent; or a cyclodextrin molecular sieve connected to a nanoparticle functionalized with a SUT or GUT targeting agent).

[0071] As used herein, the term "glucose transporter" or "GUT" refers to a fungal cell membrane anchored protein capable of transporting glucose across the cell membrane of a fungal cell. GUTs in fungi are known in the art and described herein; methods for determining substrate transport mediated by GUTs are also known in the art and described herein. For example, GUTs and their role in transporting glucose in fungi are discussed in: D Schuler et al., New Phytol. May 2015, 206(3):1086-1100.; Ozcan et al., Microbiol Mol Biol Rev. Sep 1999, 63(3):554–569.; T F dos Reis et al., PLoS One. 2013, 8(11):e81412.; W Zhang et al., Scientific Reports, Vol. 5, Article No.: 13829 (2015).; and B Wang et al., Biotechnology for Biofuels, Jan 19, 2017; 10:17. doi:10.1186 / s13068-017-0705-4.; the references are incorporated herein by reference.

[0072] In certain embodiments, the GUT protein is expressed by a fungus that is Magnaporthe oryzae, certain species of Botrytis (e.g., Botrytis cinerea), certain species of Puccinia, Fusarium graminearum, Fusarium oxysporum, Blumeria graminis, Mycosphaerella graminicola, certain species of Colletotrichum, Ustilago maydis, Melampsora lini, or Zymoseptoria tritici.

[0073] In certain embodiments, the GUT protein is an Hxt protein (eg, Hxt1 to Hxt17). In certain embodiments, the GUT protein is Hxt1 expressed in Ustilago maydis. In certain embodiments, the GUT protein is expressed by a Botrytis species (eg, Botrytis cinerea).

[0074] As used herein, the terms "a moiety or agent having affinity for GUT" or "GUT targeting moiety" or "GUT targeting agent" are used interchangeably and refer to a molecule that specifically binds to GUT and / or can be transported by GUT (e.g., transported across a membrane). However, the term "GUT targeting agent" does not include ions (protons, H ions) that can be co-transported by GUT during the transport of a molecule that specifically binds to GUT (e.g., glucose). + ). In certain embodiments, the GUT targeting agent is a small molecule compound with a molecular weight of less than 1000 g / mol (eg, <500 or <400 g / mol).

[0075] It should be understood that in addition to the cognate ligand glucose of GUT, there are other substrates or ligands that have binding affinity to the glucose transporter (GUT) and / or can be transported by the GUT of fungi. In certain embodiments, the GUT targeting agent is a monosaccharide. In certain embodiments, the GUT targeting agent is a hexose (e.g., glucose or galactose). In certain embodiments, the GUT targeting agent is glucose. In certain embodiments, the GUT targeting agent is α-D-glucose. In certain embodiments, the GUT targeting agent is β-D-glucose.

[0076] In certain embodiments, the GUT targeting agent has a higher affinity for GUT than for SUT. In certain embodiments, the GUT targeting agent has an affinity for GUT that is at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 times or more than the affinity for SUT. In certain embodiments, the GUT targeting agent has an affinity for GUT that is at least about 5 times the affinity for SUT. In certain embodiments, the GUT targeting agent has an affinity for GUT that is at least about 10 times the affinity for SUT.

[0077] In certain embodiments, the GUT transport efficiency of a GUT targeting agent is greater than the SUT transport efficiency of the targeting agent (e.g., at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 or more times more efficient).

[0078] In certain embodiments, the GUT targeting agent is not a disaccharide. In certain embodiments, the GUT targeting agent is not a SUT targeting agent. In certain embodiments, the GUT targeting agent is not sucrose.

[0079] As used herein, the term "sucrose transporter" or "SUT" refers to a membrane-anchored protein capable of transporting sucrose across a cell membrane (e.g., a cell membrane of a plant cell or a fungal cell). In certain embodiments, SUT refers to an endogenously expressed, cell membrane-anchored plant or fungal protein that is capable of transporting sucrose across the cell membrane of a plant (e.g., a monocot or dicot) or fungus. Thus, in certain embodiments, SUT is a plant SUT. In certain other embodiments, SUT is a fungal SUT. SUTs are known in the art and described herein; SUTs and their role in transporting sucrose in plants and / or fungi are discussed in the following references: J Doidy et al., Trends Plant Sci. 2012 Jul;17(7):413-22; C Kühn et al., Curr Opin Plant Biol. 2010 Jan;13(3):288-98; B Julius et al., Plant Cell Physiol. 2017 Sep 1;58(9):1442-1460; Witteck et al., J Integr Plant Biol. 2017 Jun;59(6):422-435; Wahl et al., PLoS Biol. 2010 Feb;8(2):e1000303; and Wang et al., Front Microbiol. 2020;11:591697, which are incorporated herein by reference.

[0080] In certain embodiments, the SUT protein is expressed by the phloem companion cells of the plant. In certain embodiments, the SUT protein can transport ions (e.g., protons, H + ).

[0081] In certain embodiments, the SUT protein is a SUT protein expressed by wheat, oats, corn, rice, barley, vegetables (e.g., lettuce, broccoli, carrots, spinach, or peppers), fruit plants (e.g., apples, oranges, pears, grapes, or peaches), or nut trees (e.g., almonds, walnuts, or pecans). In certain embodiments, the SUT protein is a SUT protein expressed by a weed plant. In certain embodiments, the SUT protein may phylogenetically belong to a SUT1, SUT2, SUT3, SUT4, or SUT5 clade. In certain embodiments, the SUT protein phylogenetically may belong to a SUT1 clade (e.g., in dicots). In certain embodiments, the SUT protein phylogenetically may belong to a SUT2, SUT3, SUT4, or SUT5 clade (e.g., in monocots). In certain embodiments, the SUT protein expressed by the plant is the sucrose transporter SUC2 or a plant SWEET (Sugars Will Eventually Be Exported Transporter) family member capable of transporting sucrose (eg, AtSWEET12, AtSWEET15).

[0082] In certain embodiments, the SUT protein is expressed by a fungus, which is Psora oryzae, certain species of Botrytis (e.g., Botrytis cinerea), certain species of Puccinia spp., Fusarium graminearum, Fusarium oxysporum, Blumeria graminearum, Mycosphaeria graminearum, certain species of Colletotrichum spp., Ustilago maydis, Puccinia flax, or Pseudomonas aeruginosa. In certain embodiments, the SUT protein expressed by the fungus is UmSrt1. In certain embodiments, the SUT protein is SUC2, AtSWEET12, or AtSWEET15.

[0083] As used herein, the terms "a moiety or agent having affinity for SUT" or "SUT targeting moiety" or "SUT targeting agent" are used interchangeably and refer to a molecule that specifically binds to SUT and / or can be transported (e.g., transported across a membrane) by SUT. However, the term "SUT targeting agent" does not include ions (protons, H ions) that can be co-transported by SUT during transport of a molecule that specifically binds to SUT (e.g., sucrose). + ). In certain embodiments, the SUT targeting agent is a small molecule compound with a molecular weight of less than 1000 g / mol (eg, <500 or <400 g / mol).

[0084] In certain embodiments, a SUT targeting agent (e.g., a disaccharide such as sucrose) has a higher SUT transport efficiency or has a higher affinity for SUT than a monosaccharide (e.g., glucose). In certain embodiments, a SUT targeting agent has at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 or more times the SUT transport efficiency for SUT compared to a monosaccharide. In certain embodiments, a SUT targeting agent has at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 or more times the affinity for SUT compared to a monosaccharide.

[0085] In certain embodiments, the SUT targeting agent has a higher affinity for SUT than for GUT. In certain embodiments, the SUT targeting agent has an affinity for SUT that is at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 times or more than the affinity for GUT. In certain embodiments, the SUT targeting agent has an affinity for SUT that is at least about 5 times the affinity for GUT. In certain embodiments, the SUT targeting agent has an affinity for SUT that is at least about 10 times the affinity for GUT.

[0086] In certain embodiments, the SUT targeting agent has a SUT transport efficiency that is greater than the GUT transport efficiency (e.g., at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 or more times more efficient).

[0087] In certain embodiments, the SUT targeting agent is a carbohydrate. In certain embodiments, the SUT targeting agent is a disaccharide.

[0088] As used herein, the term "disaccharide" refers to a sugar molecule having two monosaccharides joined by a glycosidic bond. Exemplary disaccharides include, but are not limited to, sucrose (one glucose and one fructose joined by a glycosidic bond) and maltose (two glucoses joined by a glycosidic bond).

[0089] In certain embodiments, the SUT targeting agent is a disaccharide comprising glucose monosaccharide. In certain embodiments, the SUT targeting agent is sucrose.

[0090] Methods for determining SUT substrate binding affinity and / or SUT-mediated transport are known in the art and described herein; Chandran et al., J Biol Chem. 2003 Nov 7; 278(45):44320-5 and Reinders et al., Plant Cell Environ. 2006 Oct; 29(10):1871-80 are incorporated herein by reference. One skilled in the art will appreciate that in addition to SUT's cognate ligand, sucrose, there are other substrates or ligands that have binding affinity for the sucrose transporter (SUT) and / or can be transported by the SUT. In certain embodiments, the SUT targeting agent is maltose.

[0091] In certain embodiments, the SUT targeting agent is a glycoside compound (eg, salicin, phenyl α-D-glucoside, or p-nitrophenyl α-D-glucoside).

[0092] In certain embodiments, the SUT targeting agent is not a monosaccharide. In certain embodiments, the SUT targeting agent is not a GUT targeting agent. In certain embodiments, the SUT targeting agent is not glucose.

[0093] As used herein, the terms "goods" or "chemical goods" are used interchangeably and refer to agents that are capable of producing a desired effect in a plant or fungus after the conjugate of the present invention is delivered to the plant or fungus. For example, a "goods" can be an agent that imparts a benefit to a plant, such as promoting the health, growth and / or disease treatment of a plant (such as a plant with desired agricultural, horticultural or forestry value). A "goods" can also be an agent that imparts a disadvantage to a plant or fungus (such as an undesirable weed (e.g., dandelion) or an invasive species that does not belong to the natural local environment). In certain embodiments, when the target plant has agricultural value or when it is necessary to suppress the target plant (e.g., a weed species) for the benefit of another plant with agricultural value, the "goods" is an agrochemical cargo. In certain embodiments, the "goods" is an agrochemical (e.g., a fungicide) in which the target fungus is undesirable. In certain embodiments, the "goods" is an agrochemical (e.g., a fungicide) in which the target fungus is associated with (e.g., contained in) a plant with agricultural value.

[0094] As used herein, the term "weed" refers to undesirable plant species in an agricultural environment (such as a farm field), e.g., grasses, dandelions, or broadleaf weeds."Weeds" typically compete with desirable plants (e.g., cash crops) for space and / or nutrients, and can be a target for elimination (e.g., by herbicides).

[0095] In certain embodiments, the cargo is a biomolecule (e.g., a protein or a nucleic acid). In certain embodiments, the cargo is a nucleic acid (e.g., a gene, siRNA, miRNA). In certain embodiments, the nucleic acid is DNA. In certain embodiments, the nucleic acid is cDNA. In certain embodiments, the nucleic acid is RNA (e.g., siRNA or miRNA). In certain embodiments, the nucleic acid is a DNA / RNA hybrid.

[0096] In certain embodiments, the nucleic acid is a pesticide described herein (eg, a fungicide, such as an RNA-based fungicide).

[0097] In certain embodiments, nucleic acids (e.g., RNA) can be connected to nanoparticles described herein (e.g., carbon dots) via electrostatic interactions. In certain embodiments, nanoparticles can have a positive surface charge or be functionalized with a material having a positive charge (e.g., a polymer coating, such as polyethyleneimine (PEI)). For example, electrostatic interactions between nanoparticles and nucleic acids are described in U.S. Patent No. 11,186,845, which is incorporated herein by reference. In certain embodiments, the cargo is a herbicide, pesticide, or fertilizer. In certain embodiments, the cargo is a herbicide or pesticide. In certain embodiments, the cargo is a pesticide. In certain embodiments, the cargo is a herbicide. In certain embodiments, the cargo is a fertilizer.

[0098] In certain embodiments, the cargo is not a biomolecule (e.g., a protein or a nucleic acid). In certain embodiments, the cargo is not a nucleic acid (e.g., DNA or RNA). In certain embodiments, the cargo is not a protein.

[0099] As used herein, the term "herbicide" refers to a chemical agent used to destroy or inhibit the growth of unwanted plants (such as weeds). Inhibition of unwanted plants may indirectly confer benefits on another plant with desired agricultural, horticultural or forestry value. A "herbicide" can be a natural or synthetic organic compound.

[0100] In certain embodiments, the herbicide is a small molecule compound having a molecular weight of less than 1000 g / mol (eg, <800 or <700 g / mol).

[0101] In certain embodiments, herbicides are polypeptides or polynucleotides that inhibit the growth of undesirable plants.

[0102] As used herein, the term "pesticide" refers to a chemical agent used to kill or inhibit pests and / or pathogens. Pests include, but are not limited to, arthropods, such as insects, arachnids, and their larvae and eggs. Pathogens include, but are not limited to, fungi, viruses, and bacteria. In certain embodiments, pests can be carriers of pathogens. Inhibiting pests and / or pathogens can promote the health and / or growth of plants, and / or treat diseases of plants infected or infected by pests and / or pathogens. In addition, pesticides can be used to inhibit fungi by direct delivery to fungi (i.e., fungi expressing SUT or GUT). "Pesticide" can be a natural or synthetic organic compound. In certain embodiments, pesticides are antimicrobial agents, such as fungicides or bactericides (e.g., antibiotic agents). In certain embodiments, pesticides are insecticides.

[0103] In certain embodiments, the pesticide is a small molecule compound having a molecular weight less than 1000 g / mol (eg, <800 or <700 g / mol).

[0104] In certain embodiments, pesticides are polypeptides or polynucleotides that kill or inhibit pests and / or pathogens.Non-limiting examples of small molecule herbicides or pesticide compounds are described in U.S. Pat. No. US10,167,483 and U.S. Pat. No. 9,095,133, which are incorporated herein by reference.

[0105] In certain embodiments, the cargo may be selected from the following list of pesticides (e.g., fungicides), which is intended to illustrate possible combinations but not to limit them:

[0106] A) Respiratory depressants

[0107] -Q oInhibitors of complex III at the site: azoxystrobin (A.1.1), coumethoxystrobin (A.1.2), coumoxystrobin (A.1.3), dimoxystrobin (A.1.4), enestroburin (A.1.5), fenaminstrobin (A.1.6), fluoxastrobin / flufenoxystrobin (A.1.7), fluoxastrobin (A.1.8), kresoxim-methyl (A.1.9), mandestrobin (A.1.10), metominostrobin (A.1.11), orysastrobin (A.1.12), picoxystrobin (A.1.13), oxazolidinone (A.1.14), oxazolidinone (A.1.15), oxazolidinone (A.1.16), oxazolidinone (A.1.17), oxazolidinone (A.1.18), oxazolidinone (A.1.19), oxazolidinone (A.1.20), oxazolidinone (A.1.21), oxazolidinone (A.1.22), oxazolidinone (A.1.23), oxazolidinone (A.1.24), oxazolidinone (A.1.25), oxazolidinone (A.1.26), oxazolidinone (A.1.27), oxazolidinone (A.1.28), oxazolidinone (A.1.29), oxazolidinone (A.1.30), oxazolidinone (A.1.31), oxazolidinone (A.1.32), oxazolidinone (A.1.33), oxazolidinone (A.1.34), oxazolidinone (A.1.35), oxazolidinone (A.1.36), oxazolidinone (A.1 3), pyraclostrobin (A.1.14), pyrametostrobin (A.1.15), pyraoxystrobin (A.1.16), trifloxystrobin (A.1.17), 2-(2-(3-(2,6-dichlorophenyl)-1-methyl-allylaminooxymethyl)-phenyl)-2-methoxyimino-N-methyl-acetamide (A.1.18), pyribencarb ( rb) (A.1.19), triclopyricarb / chlorodincarb (A.1.20), famoxadone (A.1.21), fenamidone (A.1.21), methyl-N-[2-[(1,4-dimethyl-5-phenyl-pyrazol-3-yl)oxymethyl]phenyl]-N-methoxycarbamate (A.1.22), metyltetraprole (A.1.25)

[0108] -Q iInhibitors of complex III at the site: cyazofamid (A.2.1), amisulbrom (A.2.2), [(6S,7R,8R)-8-benzyl-3-[(3-hydroxy-4-methoxypyridine-2-carbonyl)amino]-6-methyl-4,9-dioxo-1,5-dioxepane-7-yl] 2-methylpropanoate (A.2.3), fenpicoxamid (A.2.4), florylpicoxamid (A.2.5), metaylpicoxamid (A.2.6);

[0109] -Inhibitors of complex II: benodanil (A.3.1), benzovindiflupyr (A.3.2), bixafen (A.3.3), boscalid (A.3.4), carboxin (A.3.5), fenfuram (A.3.6), fluopyram (A.3.7), flutolanil (A.3.8), fluxapyroxad (A.3.9), furametpyr (A.3.10), isofetamid (A.3.11), isopyrazam (A.3.12), pyrazolamide (A.3.13), pyrazolamide (A.3.14), pyrazolamide (A.3.15), pyrazolamide (A.3.16), pyrazolamide (A.3.17), pyrazolamide (A.3.18), pyrazolamide (A.3.19), pyrazolamide (A.3.20), pyrazolamide (A.3.21), pyrazolamide (A.3.22), pyrazolamide (A.3.23), pyrazolamide (A.3.24), pyrazolamide (A.3.25), pyrazolamide (A.3.26), pyrazolamide (A.3.27), pyrazolamide (A.3.28), pyrazolamide (A.3.29), pyrazolamide (A.3.30), pyrazolamide (A.3.31), pyrazolamide (A.3.32), pyrazolamide (A.3.33), pyrazolamide (A.3.34), pyrazolamide (A.3.35), pyrazolamide (A.3.36), pyrazolamide (A.3.37), pyrazolamide (A.3.38), pyrazolamide (A.3.39), pyrazolamide (A.3.4 3.12), mepronil (A.3.13), oxycarboxin (A.3.14), penflufen (A.3.15), penthiopyrad (A.3.16), pydiflumetofen (A.3.17), pyraziflumid (A.3.18), sedaxane (A.3.19), chlorothalonil (A.3.20), thifluzamide (A.3.21), inpyrfluxam (A.3.22), pyrapropoyne (A.3.23), fluindapyr (A.3.28);

[0110] - Other respiratory inhibitors: diflumetorim (A.4.1); nitrophenyl derivatives: binapacryl (A.4.2), dinobuton (A.4.3), dinocap (A.4.4), fluazinam (A.4.5), meptyldinocap (A.4.6), ferimzone (A.4.7); organometallic compounds: triphenyltin salts, such as triphenyltin acetate (fentin-acetate) (A.4.8), triphenyltin chloride (fentin chloride) (A.4.9) or triphenyltin hydroxide (fentinhydroxide) (A.4.10); ametoctradin (A.4.11); silthiofam (Silthiofam) (A.4.12);

[0111] B) Sterol biosynthesis inhibitors (SBI fungicides)

[0112] -C14 demethylase inhibitors: triazoles: azaconazole (B.1.1), bitertanol (B.1.2), bromuconazole (B.1.3), cyproconazole (B.1.4), difenoconazole (B.1.5), diniconazole (B.1.6), diniconazole-M (B.1.7), epoxiconazole (B.1.8), fenbuconazole (B.1.9), fluquinconazole (fl uquinconazole (B.1.10), flusilazole (B.1.11), flutriafol (B.1.12), hexaconazole (B.1.13), imibenconazole (B.1.14), ipconazole (B.1.15), metconazole (B.1.17), myclobutanil (B.1.18), oxpoconazole (B.1.19), paclobutrazol (B.1.20), oxadiazole (B.1.21), oxadiazole (B.1.22), oxadiazole (B.1.23), oxadiazole (B.1.24), oxadiazole (B.1.25), oxadiazole (B.1.26), oxadiazole (B.1.27), oxadiazole (B.1.28), oxadiazole (B.1.29), oxadiazole (B.1.30), oxadiazole (B.1.31), oxadiazole (B.1.32), oxadiazole (B.1.33), oxadiazole (B.1.34), oxadiazole (B.1.35), oxadiazole (B.1.36), oxadiazole (B.1.37), oxadiazole (B.1.38), oxadiazole (B.1.39), oxadiazole (B.1.40), oxadiazole (B.1.41), oxadiazole (B.1.42), oxadiazole (B.1.43), oxadiazole (B.1.44), oxadiazole (B.1.45), oxadiazole (B.1.46), oxadiazole (B.1.47), oxadiazole (B.1.48), oxadiazole (B.1.49), oxadiazole (B.1 le)(B.1.20), penconazole(B.1.21), propiconazole(B.1.22), prothioconazole(B.1.23), simeconazole(B.1.24), tebuconazole(B.1.25), tetraconazole(B.1.26), triadimefon(B.1.27), triadimenol(B.1.28), triticonazole(B.1.29), B.1.29), uniconazole (B.1.30), 2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazolyl-1-yl)-1-[5-[4-(2,2,2-trifluoroethoxy)phenyl]-2-pyridyl]propan-2-ol (B.1.31), 2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazolyl-1-yl)-1-[5-[4-(trifluoromethoxy)phenyl]-2-pyridyl]propan-2-ol (B.1.32), fluoxytioconazole (B.1.33), ipfentrifluconazole (B.1.34), 2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazolyl-1-yl)-1-[5-[4-(trifluoromethoxy)phenyl]-2-pyridyl]propan-2-ol (B.1.35), 2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazolyl-1-yl)-1-[5-[4-(trifluoromethoxy)phenyl]-2-pyridyl]propan-2-ol (B.1.36), 2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazolyl-1-yl)-1-[5-[4-(trifluoromethoxy)phenyl]-2-pyridyl]propan-2-ol (B.1.37), 2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazolyl-1-yl)-1-[5-[4-(trifluoromethoxy)phenyl]-2-pyridyl]propan-2-ol (B.1.38), 2-(2,4-difluorophenyl)-1,1-difluoro-3-(tetrazolyl37), mefentrifluconazole (B.1.38); imidazoles: imazalil (B.1.44), pefurazoate (B.1.45), prochloraz (B.1.46), triflumizole (B.1.47); pyrimidines, pyridines, piperazines: fenarimol (B.1.49), pyrifenox (B.1.50), triforine (B.1.51),.

[0113] -δ14-reductase inhibitors: aldimorph (B.2.1), dodemorph (B.2.2), dodemorph-acetate (B.2.3), fenpropimorph (B.2.4), tridemorph (B.2.5), fenpropidin (B.2.6), piperalin (B.2.7), spiroxamine (B.2.8);

[0114] -3-Ketoreductase inhibitors: fenhexamid (B.3.1);

[0115] - Other sterol biosynthesis inhibitors: chlorphenomizole (B.4.1);

[0116] C) Nucleic acid synthesis inhibitors

[0117] - Phenylamide or acylamino acid fungicides: benalaxyl (C.1.1), benalaxyl-M (C.1.2), kiralaxyl (C.1.3), metalaxyl (C.1.4), metalaxyl-M (C.1.5), ofurace (C.1.6), oxadixyl (C.1.7);

[0118] - Other nucleic acid synthesis inhibitors: hymexazole (C.2.1), octhilinone (C.2.2), oxolinic acid (C.2.3), bupirimate (C.2.4), 5-fluorocytosine (C.2.5), 5-fluoro-2-(p-tolylmethoxy)pyrimidine-4-amine (C.2.6), 5-fluoro-2-(4-fluorophenylmethoxy)pyrimidine-4-amine (C.2.7), 5-fluoro-2-(4-chlorophenylmethoxy)pyrimidine-4-amine (C.2.8);

[0119] D) Inhibitors of cell division and cytoskeleton

[0120] - Tubulin inhibitors: benomyl (D.1.1), carbendazim (D.1.2), fuberidazole (D1.3), thiabendazole (D.1.4), thiophanate-methyl (D.1.5), pyridachlometyl (D.1.6), N-ethyl-2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]butyramide (D.1.8);

[0121] - Other cell division inhibitors: diethofencarb (D.2.1), ethaboxam (D.2.2), pencycuron (D.2.3), fluopicolide (D.2.4), zoxamide (D.2.5), metrafenone (D.2.6), pyriofenone (D.2.7), phenamacril (D.2.8);

[0122] E) Amino Acids and Protein Synthesis Inhibitors

[0123] -Methionine synthesis inhibitors: cyprodinil (E.1.1), mepanipyrim (E.1.2), pyrimethanil (E.1.3);

[0124] - Protein synthesis inhibitors: blasticidin-S (E.2.1), kasugamycin (E.2.2), kasugamycin hydrochloride-hydrate (E.2.3), mildiomycin (E.2.4), streptomycin (E.2.5), oxytetracyclin (E.2.6);

[0125] F) Signal transduction inhibitors

[0126] -MAP / histidine kinase inhibitors: fluoroimid (F.1.1), iprodione (F.1.2), procymidone (F.1.3), vinclozolin (F.1.4), fludioxonil (F.1.5);

[0127] - G protein inhibitor: quinoxyfen (F.2.1);

[0128] G) Lipid and membrane synthesis inhibitors

[0129] - Phospholipid biosynthesis inhibitors: edifenphos (G.1.1), iprobenfos (G.1.2), pyrazophos (G.1.3), isoprothiolane (G.1.4);

[0130] -Lipid peroxidation: dicloran (G.2.1), quintozene (G.2.2), tecnazene (G.2.3), tolclofos-methyl (G.2.4), biphenyl (G.2.5), chloroneb (G.2.6), etridiazole (G.2.7), zinc thiazole (G.2.8);

[0131] - Phospholipid biosynthesis and cell wall deposition: dimethomorph (G.3.1), flumorph (G.3.2), mandipropamid (G.3.3), pyrimorph (G.3.4), benthiavalicarb (G.3.5), iprovalicarb (G.3.6), valifenalate (G.3.7);

[0132] - Compounds and fatty acids that affect cell membrane permeability: propamocarb (G.4.1);

[0133] - Oxysterol binding protein inhibitors: oxathiapiprolin (G.5.1), fluoxapiprolin (G.5.3)

[0134] H) Inhibitors with multi-site action

[0135] - Inorganic active substances: Bordeaux mixture (H.1.1), copper (H.1.2), copper acetate (H.1.3), copper hydroxide (H.1.4), copper oxychloride (H.1.5), basic copper sulfate (H.1.6), sulfur (H.1.7);

[0136] -Thio- and dithiocarbamates: ferbam (H.2.1), mancozeb (H.2.2), maneb (H.2.3), metam (H.2.4), metiram (H.2.5), propineb (H.2.6), thiram (H.2.7), zineb (H.2.8), ziram (H.2.9);

[0137] -Organochlorine compounds: anilazine (H.3.1), chlorothalonil (H.3.2), captafol (H.3.3), captan (H.3.4), folpet (H.3.5), dichlofluanid (H.3.6), dichlorophen (H.3.7), hexachlorobenzene (H.3.8), pentachlorophenol (H.3.9) and its salts, phthalide (H.3.10), tolylfluanid (H.3.11);

[0138] -Guanidine and others: guanidine (H.4.1), dodine (H.4.2), dodine free base (H.4.3), guazatine (H.4.4), guazatine-acetate (H.4.5), iminoctadine (H.4.6), iminoctadine-triacetate (H.4.7), iminoctadine-tris(albesilate) (H.4.8), dithianon (H.4.9),

[0139] I) Cell wall synthesis inhibitors

[0140] - Glucan synthesis inhibitors: validamycin (I.1.1), polyoxin B (I.1.2);

[0141] - Melanin synthesis inhibitors: pyroquilon (I.2.1), tricyclazole (I.2.2), carpropamid (I.2.3), dicyclomine (I.2.4), fenoxanil (I.2.5);

[0142] J) Plant defense inducers

[0143] - acibenzolar-S-methyl (J.1.1), probenazole (J.1.2), isotianil (J.1.3), tiadinil (J.1.4), prohexadione-calcium (J.1.5); phosphonates: fosetyl (J.1.6), fosetyl-aluminum (J.1.7), phosphorous acid and its salts (J.1.8), calcium phosphonate (J.1.11), potassium phosphonate (J.1.12), potassium bicarbonate or sodium bicarbonate (J.1.9), 4-cyclopropyl-N-(2,4-dimethoxyphenyl)thiadiazole-5-carboxamide (J.1.10);

[0144] K) Unknown mode of action

[0145] -bronopol (K.1.1), chinomethionat (K.1.2), cyflufenamid (K.1.3), cymoxanil (K.1.4), dazomet (K.1.5), debacarb (K.1.6), diclocymet (K.1.7), diclomezine (K.1.8), difenzoquat (K.1.9), difenzoquat-methylsulfate (K.1.10), diphenylamine (K.1.11), fenitropan (K.1.12), fenpyrazamine (K.1.13), flumetover (K.1.14), flumetyls ulforim) (K.1.60), flusulfamide (K.1.15), flutianil (K.1.16), harpin (K.1.17), methasulfocarb (K.1.18), nitrapyrin (K.1.19), nitrothal-isopropyl (K.1.20), tolprocarb (K.1.21), oxin-copper (K.1.22), proquinazid (K.1.23), seboctylamine (K.1.61), tebufloquin (K.1.24), tecloftalam (K.1.25), and triazoxide (K.1.26).

[0146] In certain embodiments, the cargo is selected from the group consisting of chlorpyrifos, methylviologen, oxyfluorfen, imazaquin, fluthiacet, diclofop, penoxsulam, norflurazon, trifludimoxazin, picolinafen, pyraclostrobin, boscalid, and acifluorfen.

[0147] In certain embodiments, the cargo is selected from the group consisting of allyl isothiocyanate, chlorpyrifos, methyl viologen, naphthalene, 4-chloro-2-methylphenoxyacetic acid (MCPA), norflurazon, and carbofuran.

[0148] In certain embodiments, the cargo is a fungicide that is a small molecule compound with a molecular weight of less than 1000 g / mol (eg, <800 or <700 g / mol).

[0149] In certain embodiments, the fungicide is selected from the group consisting of oxazolidinone, benzathiapiprolin, thiophanate-methyl, cyazofamid, ethersstrobin, etaconazole, fluopyram, myclobutanil, fluthiazolin, pyraclostrobin, thiabendazim, and spiroxabiocin.

[0150] In certain embodiments, the fungicide is selected from the group consisting of oxazolidinone, benzathiapiprolin, ethiconazole, fluopyram, fluthiapyram, and spiroxabiocin.

[0151] In certain embodiments, the fungicide is a polypeptide or polynucleotide that kills or inhibits a fungal pathogen.

[0152] As used herein, the term "fertilizer" refers to a chemical agent used for its nutritional value to promote the health or growth of plants. A "fertilizer" can be an organic compound or an inorganic compound.

[0153] As used herein, the term "molecular basket" refers to cyclodextrin. Cyclodextrin is a family of cyclic oligosaccharides consisting of a macrocycle of glucose subunits (e.g., about 6-8 glucose subunits) joined by α-1,4 glycosidic bonds. Examples of molecular baskets include α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin.

[0154] In certain embodiments, the molecular basket includes α-cyclodextrin, β-cyclodextrin or γ-cyclodextrin. In certain embodiments, the molecular basket is α-cyclodextrin, β-cyclodextrin or γ-cyclodextrin. The chemical cargo described herein can form a complex with the molecular basket (e.g., loaded into the molecular basket). The molecular basket can be directly or indirectly connected to the SUT or GUT targeting agent. The molecular basket can also be directly or indirectly connected to the nanoparticle (e.g., the molecular basket can be included in the linker group). The molecular basket may include groups including but not limited to -COOH, amines, thiols, azides, maleimides or boronic acids, which are used to connect to SUT or GUT targeting agents and / or nanoparticles. Exemplary cyclodextrins with such functional groups include but are not limited to succinyl-β-cyclodextrin, mono-(6-ethylenediamine-6-deoxy)-β-cyclodextrin or mono-(6-thiol-6-deoxy)-β-cyclodextrin.

[0155] As used herein, the term "nanoparticle" or "nanomaterial" refers to a nanoparticle or nanomaterial selected from the group consisting of quantum dots, carbon dots, carbon nanotubes (e.g., single-walled carbon nanotubes (SWCNTs)), silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, metal or metal oxide nanoparticles (e.g., gold, silver, copper, zinc, zinc oxide, magnesium, magnesium oxide, cerium oxide, or iron oxide nanoparticles), and macro- or micronutrient-based nanoparticles (e.g., nitrogen, phosphorus, copper, zinc, magnesium, etc.). In certain embodiments, the "nanoparticle" or "nanomaterial" has a size in the range of about 1 nm to 1000 nm. For example, nanostructures (e.g., nanoparticles) can have a longest dimension (e.g., diameter) in the range of about 1 to 900 nm, 1 to 800 nm, 1 to 700 nm, 1 to 600 nm, 1 to 500 nm, 1 to 400 nm, 1 to 300 nm, 1 to 250 nm, 1 to 200 nm, 1 to 150 nm, 1 to 100 nm, 1 to 90 nm, 1 to 80 nm, 1 to 70 nm, 1 to 60 nm, 1 to 50 nm, 1 to 40 nm, 1 to 30 nm, 1 to 25 nm, 1 to 20 nm, 1 to 15 nm, 1 to 10 nm, or 1 to 5 nm." nanoparticles" or "nanomaterials" can be approximately spherical or non-spherical. Methods for characterizing nanoparticles or nanomaterials are known in the art and are described herein (e.g., electron microscopy, dynamic light scattering, or atomic force microscopy).

[0156] In certain embodiments, the nanoparticle or nanomaterial can carry cargo. For example, the cargo can be loaded (e.g., encapsulated or distributed) within the nanoparticle, such as loaded in a lipid nanoparticle or liposome (in the lipid layer and / or in the aqueous core of the liposome). However, the cargo can also be conjugated or connected to the surface of the nanoparticle.

[0157] In certain embodiments, the nanoparticle surface (eg, carbon dots, see FIG. 1 ) can be dually functionalized with a cyclodextrin molecular basket and a SUT targeting agent (eg, sucrose), wherein the cargo can be loaded within the cyclodextrin molecular basket.

[0158] In certain embodiments, the nanoparticle surface (eg, carbon dots, see FIG. 14 ) can be dually functionalized with a cyclodextrin molecular basket and a GUT targeting agent (eg, glucose), wherein the cargo can be loaded within the cyclodextrin molecular basket.

[0159] In certain embodiments, the nanoparticle is a quantum dot, a carbon dot, a carbon nanotube, a silica nanoparticle (e.g., a porous silica nanoparticle), a metal or metal oxide nanoparticle, a lipid nanoparticle, or a liposome.

[0160] In certain embodiments, the nanoparticles are carbon dots, carbon nanotubes, silica nanoparticles (eg, porous silica nanoparticles), metal or metal oxide nanoparticles, lipid nanoparticles, or liposomes.

[0161] In certain embodiments, the nanoparticles are carbon dots, carbon nanotubes, silica nanoparticles (eg, porous silica nanoparticles), lipid nanoparticles, or liposomes.

[0162] In certain embodiments, the nanoparticles are carbon dots, carbon nanotubes, or silica nanoparticles (eg, porous silica nanoparticles).

[0163] In certain embodiments, the nanoparticles are quantum dots. In certain embodiments, the nanoparticles are not quantum dots.

[0164] In certain embodiments, the nanoparticles are carbon dots. In certain embodiments, the nanoparticles are not carbon dots.

[0165] In certain embodiments, the nanoparticles are silica nanoparticles (eg, mesoporous silica nanoparticles). In certain embodiments, the nanoparticles are not silica nanoparticles.

[0166] In some embodiments, the nanoparticles are metal or metal oxide nanoparticles (e.g., gold, silver, copper, zinc, zinc oxide, magnesium, magnesium oxide, cerium oxide, or iron oxide nanoparticles). In some embodiments, the nanoparticles are not metal or metal oxide nanoparticles (e.g., gold, silver, or iron oxide nanoparticles).

[0167] In certain embodiments, the nanoparticles are carbon dots containing metals (eg, metal-doped carbon dots). In certain embodiments, the nanoparticles are carbon dots that do not contain metals.

[0168] In some embodiments, the nanoparticles are micro- or macronutrient-based nanoparticles that can be used as nanofertilizers to supplement plants with macro- or micronutrients (e.g., nitrogen, phosphorus, copper, zinc, or magnesium). In some embodiments, the nanoparticles are phosphorus nanofertilizers, such as nano-sized hydroxyapatite (Ca 5 (PO 4 ) 3 OH). In certain embodiments, the nanoparticles are urea-modified hydroxyapatite nanoparticles. In certain embodiments, the nanoparticles are not macro- or micronutrient-based nanoparticles.

[0169] Methods for surface modification of nanoparticles (e.g., hydroxyapatite, metal or metal oxide nanoparticles) are known in the art and described herein. In certain embodiments, the surface of the hydroxyapatite, metal or metal oxide nanoparticles may have a layer of silicon dioxide coating (SiO 2 In certain embodiments, the surface of the hydroxyapatite, metal or metal oxide nanoparticles can be functionalized with a linker as described herein, including a silane molecule or a polymer such as PEG, which can be further functionalized with a SUT targeting agent as described herein (e.g., sucrose).

[0170] In certain embodiments, the nanoparticle is a lipid nanoparticle or a liposome. In certain embodiments, the nanoparticle is not a lipid nanoparticle or a liposome.

[0171] As used herein, the term "connection" refers to two elements being bonded in a functional relationship. For example, "connection" may refer to cargo (e.g., herbicides or pesticides) and targeting agents (e.g., SUT targeting agents, such as sucrose; or GUT targeting agents, such as glucose) being bonded in a functional relationship. The term "connection" also refers to the bonding / association of two chemical moieties, which makes the position or biodistribution of one chemical moiety possibly affected by another chemical moiety. For example, cargo is referred to as being "connected to" or "associated with" a targeting moiety, wherein after the cargo is introduced into a plant or fungus in need, the cargo enters the plant / fungus and the transport / biodistribution inside the plant / fungus is affected by the connected targeting moiety. Therefore, as used herein, the functional relationship between cargo and the connected targeting moiety may involve co-transport and / or co-localization in certain plant compartments (e.g., leaves, stems, roots, or vascular systems, such as phloem) or fungal compartments during certain stages of transport.

[0172] The cargo can be linked to the targeting moiety directly or indirectly. When the cargo molecule is covalently bonded to the targeting agent, the cargo is said to be directly linked to the targeting agent.

[0173] When the cargo is connected to the targeting agent by, for example, a linker and / or other material (e.g., NP or cyclodextrin), the cargo is said to be indirectly connected to the targeting agent. For example, the cargo can be loaded in a nanoparticle or a cyclodextrin molecular basket, and the nanoparticle or molecular basket is functionalized with a targeting moiety. Therefore, in certain embodiments, although the cargo may not be covalently linked to the targeting moiety, the cargo is "connected to" the targeting moiety or associated with the targeting moiety through the nanoparticle and / or molecular basket. In certain embodiments, the cargo is loaded in a molecular basket, which is directly or indirectly connected to the nanoparticle, and wherein the nanoparticle is directly or indirectly connected to the targeting agent.

[0174] Thus, in certain embodiments, cargo is indirectly linked to a targeting agent via nanoparticles and / or cyclodextrin molecular baskets. In certain embodiments, cargo is indirectly linked to a SUT targeting agent via nanoparticles and / or cyclodextrin molecular baskets. In certain embodiments, cargo is indirectly linked to a GUT targeting agent via nanoparticles and / or cyclodextrin molecular baskets.

[0175] In certain embodiments, the cargo is loaded within a nanoparticle or a cyclodextrin molecular basket.

[0176] In certain embodiments, the cargo is loaded within the nanoparticle.

[0177] In certain embodiments, the cargo is loaded within a cyclodextrin molecular basket.

[0178] In certain embodiments, the cargo is conjugated to the surface of the nanoparticle.

[0179] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula I:

[0180] NP—(Connector—TA) n

[0181] (Formula I)

[0182] Wherein: NP is a nanoparticle; TA is a sucrose transporter (SUT) targeting agent or a glucose transporter (GUT) targeting agent; the linker has a molecular weight of about 20 Daltons to about 20,000 Daltons; and n is an integer ≥ 1. In certain embodiments, TA is a SUT targeting agent. In certain embodiments, TA is a GUT targeting agent. In certain embodiments, the conjugate comprises a mixture of SUT and GUT targeting agents.

[0183] As described herein, nanoparticles (NPs) have a surface area that can be functionalized with one or more targeting agents. For example, an integer "n" indicates that the surface of the nanoparticle may include multiple linkers-SUT targeting agents (e.g., linkers-sucrose) or multiple linkers-GUT targeting agents (e.g., linkers-glucose). Therefore, the conjugates described herein may include nanoparticles (NPs) connected to one or more sucrose transporters (SUT) targeting agents (which may be the same or different SUT targeting agents). That is, the surface of the NP may be coated with "n" copies of SUT targeting agents (e.g., sucrose). Alternatively, some conjugates described herein may include nanoparticles (NPs) connected to one or more glucose transporters (GUT) targeting agents (which may be the same or different GUT targeting agents). Therefore, the surface of the NP may be coated with "n" copies of GUT targeting agents (e.g., glucose). In certain embodiments, the surface of the NP may be coated with "n" copies of SUT targeting agents (e.g., sucrose) and GUT targeting agents (e.g., glucose). Depending on the NP size and surface functionalization reaction, the copy number of the targeting agent present on the NP surface may be different. In certain embodiments, "n" is about 10, 10 2 , 10 3 , 10 4 , 10 5 , 10 6 , 10 7 , 10 8 , 10 9 In certain embodiments, "n" is about 1 to 10 9 , 1 to 10 8 , 1 to 10 7 , 1 to 10 6 , 1 to 10 5 , 1 to 10 4 , 1 to 10 3 , 1 to 10 2 or 1 to 10. In certain embodiments, "n" is about 1 to 10 6 or 10 to 10 4 .

[0184] In certain embodiments, the nanoparticles are selected from the group consisting of carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, metal or metal oxide nanoparticles, and micro- or macronutrient-based nanoparticles.

[0185] In certain embodiments, the nanoparticles are selected from the group consisting of carbon dots, carbon nanotubes, silica nanoparticles (eg, porous silica nanoparticles), lipid nanoparticles, liposomes, and metal or metal oxide nanoparticles.

[0186] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula Ia:

[0187] NP—(Linker—Sucrose) n (Formula Ia).

[0188] In certain embodiments, one end of the linker comprises a boronic acid group that binds to a SUT targeting agent (eg, a disaccharide such as sucrose).

[0189] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula Ia':

[0190] NP—(Linker—Glucose) n (Formula Ia').

[0191] In certain embodiments, one end of the linker comprises a boronic acid group that binds to a GUT targeting agent (eg, a monosaccharide such as glucose).

[0192] In certain embodiments, the "linked" cargo and SUT targeting agent or GUT targeting agent are co-localized within the formulation prior to introduction into the target plant or fungus, or once introduced into the plant / fungus, are co-localized within the plant / fungus during certain transport stages (e.g., from the leaf surface to transport to the leaf phloem veins), such that the distance between the cargo and the linked targeting agent is typically in the micron / submicron range. The distance between the cargo and the linked targeting moiety may depend on the arrangement of the cargo targeting moiety, such as the size of the linker and / or the size of the nanoparticle. For example, the distance between the cargo and the attached targeting agent can be in the range of about 1 nm to 1000 nm, 1 nm to 900 nm, 1 nm to 800 nm, 1 nm to 700 nm, 1 nm to 600 nm, 1 nm to 500 nm, 1 nm to 400 nm, 1 nm to 300 nm, 1 nm to 200 nm, 1 nm to 100 nm, 1 nm to 90 nm, 1 nm to 80 nm, 1 nm to about 70 nm, 1 nm to 60 nm, 1 nm to 50 nm, 1 nm to about 40 nm, 1 nm to 30 nm, 1 nm to 20 nm, 1 nm to 10 nm, or 1 nm to 5 nm.

[0193] In certain embodiments, the cargo and the attached targeting moiety may be co-localized within about 1000nm, 900nm, 800nm, 700nm, 600nm, 500nm, 400nm, 300nm, 200nm, 100nm, 90nm, 80nm, 70nm, 60nm, 50nm, 40nm, 30nm, 20nm, 10nm, 9nm, 8nm, 7nm, 6nm, 5nm, 4nm, 3nm, 2nm, 1nm or less of each other during the initial phase of transport of the substance once introduced into the plant or fungus.

[0194] In certain embodiments, nanoparticles or conjugates described herein (e.g., conjugates of Formula I) have a diameter of about 5nm, 10nm, 15nm, 20nm, 25nm, 30nm, 40nm, 50nm, 60nm, 70nm, 80nm, 90nm, 100nm, 150nm, 200nm, 250nm, 300nm, 400nm, 500nm, 600nm, 700nm, 800nm, 900nm, or 1000nm. In certain embodiments, nanoparticles or conjugates described herein have a diameter of about 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, or 300nm. In certain embodiments, nanoparticles described herein or conjugates have a diameter of about 5nm, 10nm, 15nm, 20nm, 25nm, 30nm, 40nm, 50nm, 60nm, 70nm, 80nm, 90nm or 100nm. In certain embodiments, nanoparticles described herein or conjugates have a diameter of about 15nm, 20nm, 25nm, 30nm, 40nm, 50nm, 60nm or 70nm. In certain embodiments, nanoparticles described herein or conjugates have a diameter of about 5, 10, 15, 20, 25, 30 or 40nm.

[0195] In some embodiments, the nanoparticles or conjugates described herein (e.g., conjugates of Formula I) have a diameter range of about 1 to 1000 nm, 1 nm to 900 nm, 1 nm to 800 nm, 1 nm to 700 nm, 1 nm to 600 nm, 1 nm to 500 nm, 1 nm to 400 nm, 1 nm to 300 nm, 1 nm to 200 nm, 1 nm to 100 nm, 1 nm to 90 nm, 1 nm to 80 nm, 1 nm to 70 nm, 1 nm to 60 nm, 1 nm to 50 nm, 1 nm to about 40 nm, 1 nm to 30 nm, 1 nm to 20 nm, 1 nm to 10 nm, or 1 nm to 5 nm. In certain embodiments, nanoparticles described herein or conjugates have a diameter range of about 5nm to 400nm, 5nm to 350nm, 5nm to 300nm, 5nm to 250nm, 5nm to 200nm, 5nm to 150nm, 5nm to 100nm, 5nm to 90nm, 5nm to 80nm, 5nm to 70nm, 5nm to 60nm, or 5nm to 50nm. In certain embodiments, nanoparticles described herein or conjugates may have a diameter range of about 1nm to 200nm, 5nm to 150nm, 10nm to 120nm, 15nm to 100nm, or 20nm to 90nm. In certain embodiments, nanoparticles described herein or conjugates may have a diameter range of about 1nm to 40nm, 5nm to 40nm, 10 to 40nm, 15 to 40nm, 20 to 40nm, or 25 to 40nm. In certain embodiments, the nanoparticles or conjugates described herein may have a diameter ranging from about 5 nm to 15 nm, 10 nm to 25 nm, 15 to 30 nm, or 20 to 50 nm.

[0196] In certain embodiments, the nanoparticles or conjugates described herein may have a diameter of at least about 5 nm, 10 nm, 15 nm, 20 nm, 25 nm, 30 nm, or more (e.g., at least 5 nm, 10 nm, or 15 nm).

[0197] In certain embodiments, the nanoparticles or conjugates described herein may have a diameter of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 nm. In certain embodiments, the nanoparticles or conjugates described herein may have a diameter of at least about 3 nm, 4 nm, 5 nm, 6 nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, 15 nm, 16 nm, 17 nm, 18 nm, or more.

[0198] In certain embodiments, the diameter of the nanoparticle or conjugate is a hydrodynamic diameter (e.g., determined by dynamic light scattering). In certain embodiments, the diameter of the nanoparticle or conjugate is determined by electron microscopy. In certain embodiments, the diameter of the nanoparticle or conjugate is determined by atomic force microscopy (AFM).

[0199] In certain embodiments, the nanoparticles or conjugates described herein (e.g., conjugates of Formula I) may have a negative zeta potential of about -5 to -90, -10 to -80, -15 to -70, or -20 to -60 mV. In certain embodiments, the nanoparticles or conjugates described herein (e.g., conjugates of Formula I) may have a negative zeta potential of about -5, -10, -15, -20, -30, -40, -50, -60, or -70 mV. In certain embodiments, the nanoparticles or conjugates described herein (e.g., conjugates of Formula I) may have a negative zeta potential of at least about -5, -10, -15, -20, -30, -40, -50, -60, -70 mV or a negative zeta potential absolute value of greater (e.g., at least -20 or -30 mV).

[0200] In certain embodiments, the nanoparticles or conjugates described herein (e.g., conjugates of Formula I) may have a positive zeta potential of about 5 to 90, 10 to 80, 15 to 70, or 20 to 60 mV. In certain embodiments, the nanoparticles or conjugates described herein (e.g., conjugates of Formula I) may have a positive zeta potential of about 5, 10, 15, 20, 30, 40, 50, 60, or 70 mV. In certain embodiments, the nanoparticles or conjugates described herein (e.g., conjugates of Formula I) may have a positive zeta potential of at least about 5, 10, 15, 20, 30, 40, 50, 60, 70 mV or more (e.g., at least 20 or 30 mV).

[0201] As used herein, the term "linker" or "linking moiety" refers to a functional group that covalently bonds two or more parts of a compound or material. For example, a linking moiety can be used to covalently bond a SUT targeting agent to a cargo, a nanoparticle, and / or a molecular basket. A linking moiety can be used to covalently bond a GUT targeting agent to a cargo, a nanoparticle, and / or a molecular basket. Similarly, a linking moiety can be used to covalently bond a molecular basket to a nanoparticle. Useful bonds for connecting linking moieties to compounds and other materials include, but are not limited to, amide bonds, amine bonds, ester bonds, carbamate bonds, urea bonds, thioether bonds, thiocarbamate bonds, thiocarbonate bonds, thiourea bonds, siloxane bonds, and boron oxygen bonds. For example, exemplary useful bonds may include boron oxygen bonds-B(R c ) 2 , where R c Each is O-; and siloxane bond -Si(R b) 3 , where R b Each independently is -OH, O- or (C 1- C 4 )alkoxy, each O- in the siloxane bond can be bonded to the surface of the silica nanoparticle or can be bonded to an adjacent Si atom. In certain embodiments, the boron oxygen bond is -B(O-) 2 .

[0202] In certain embodiments, the linker comprises a boronic acid group -B(O-) 2 , where each O- is bonded to a targeting agent (TA).

[0203] In certain embodiments, the linker has a molecular weight of about 20 Daltons to about 20,000 Daltons.

[0204] In certain embodiments, the linker has a molecular weight of about 20 Daltons to about 10,000 Daltons.

[0205] In certain embodiments, the linker has a molecular weight of about 20 Daltons to about 5,000 Daltons.

[0206] In certain embodiments, the linker has a molecular weight of about 20 Daltons to about 3,000 Daltons.

[0207] In certain embodiments, the linker has a molecular weight of about 20 Daltons to about 2,000 Daltons.

[0208] In certain embodiments, the linker has a molecular weight of about 20 Daltons to about 1,000 Daltons.

[0209] In certain embodiments, the boron oxygen bond can form a bidentate bond with two hydroxyl groups (eg, syn-periplanar dihydroxyl groups) of the carbohydrate moiety.

[0210] In certain embodiments, one end of the linker comprises a boronic acid group that binds to a SUT targeting agent (eg, a disaccharide such as sucrose).

[0211] In certain embodiments, one end of the linker comprises a boronic acid group that binds to a GUT targeting agent (eg, a monosaccharide such as glucose).

[0212] In certain embodiments, the linker or connecting moiety comprises a divalent, saturated or unsaturated, branched or unbranched (C 2- C 18 ) hydrocarbon chain, wherein one or more carbons of the hydrocarbon chain are optionally replaced by -O-, -N(R s )-, -S-, aryl (e.g., -C 6 H 4-) or heteroaryl, and wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, thiol, oxo (=O) and thio (=S); and R s H or (C 1- C 6 )alkyl.

[0213] In certain embodiments, the linker has the structure -XYZ-:

[0214] X is a bond, -O-, -S-, -C(=O)-, -N(R a )-, -C(=O)NH-, -C(=S)NH-, -C(=O)O-, -C(=O)S-, -NHSO 2 -, -OC(=O)NH-, -NHC(=O)NH-, -NHC(=S)NH-, -Si(R b ) 3 or -B(R c ) 2 ,

[0215] Z is a bond, -O-, -S-, -C(=O)-, -N(R a )-, -C(=O)NH-, -C(=S)NH-, -C(=O)O-, -C(=O)S-, -NHSO 2 -, -OC(=O)NH-, -NHC(=O)NH-, -NHC(=S)NH-, -Si(R b ) 3 , or -B(R c ) 2 ;

[0216] R a H or (C 1 -C 6 )alkyl;

[0217] Each R b are independently O-, -OH or (C 1- C 4 ) alkoxy;

[0218] Each R c is O- connected to TA;

[0219] Y is a divalent, saturated or unsaturated, branched or unbranched chain (C 2- C 18 ) hydrocarbon chain, wherein one or more carbons of the hydrocarbon chain are optionally replaced by -O-, -N(R s )-, -S-, aryl (e.g., -C 6 H 4-) or heteroaryl, and wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, thiol, oxo (=O) and thio (=S); and R s H or (C 1- C 6 )alkyl.

[0220] In certain embodiments, X is -Si(R b ) 3 .

[0221] In certain embodiments, Z is -B(O-) 2 .

[0222] In certain embodiments, the linker or connecting moiety comprises a 2 CH 2 ) m -a polyethylene glycol (PEG) segment, wherein m is an integer from 2 to 120 (e.g., m is 24, 43, 80, or 113). For example, the linker or connecting portion may comprise a PEG segment of PEG(400), PEG(600), PEG(1000), PEG(2000), or PEG(5000).

[0223] In certain embodiments, the linker may comprise a PEG portion as described above and a hydrocarbon chain portion, wherein the hydrocarbon chain portion is capable of anchoring to the nanoparticle. For example, the linker may comprise a PEG portion and a chain (e.g., C 2-8 Examples of such non-limiting exemplary linkers include Si(R b ) 3 -(CH 2 ) n -PEG-, or Si(R b ) 3 -(CH 2 ) 3 -NHC(=O)NH-(CH 2 ) 2 -PEG-, or -S-(CH 2 ) n -PEG-, or -S-(CH 2 ) 2 -C(=O)NH-(CH 2 ) 2 -PEG-, wherein the alkyl chain can be anchored to the silica nanoparticles via a siloxane bond, or can be anchored to the metal nanoparticles via a thiol bond, and the PEG can be functionalized, for example, with amines, carboxyls or boronic acids as described above, to conjugate with a targeting moiety.

[0224] In certain embodiments, the linker can be an amphiphilic linker comprising a relatively hydrophilic portion (e.g., PEG) and a hydrophobic portion, wherein the hydrophobic portion is capable of partitioning into the nanoparticle. For example, the linker can comprise a PEG portion and a hydrophobic portion of a lipid tail capable of partitioning into the lipid layer of a lipid nanoparticle or liposome, such non-limiting exemplary linkers include phospholipid derivatives (e.g., phospholipid-PEG-), such as 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-polyethylene glycol (DSPE-PEG-) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-polyethylene glycol (DOPE-PEG-), wherein PEG can be functionalized, for example, with an amine, carboxyl or boronic acid as described above to conjugate with a targeting moiety.

[0225] In certain embodiments, the linker comprises a phenylboronic acid (PBA) group. In certain embodiments, the linker is -(C 6 H 4 )-B(O-) 2 End-capping.

[0226] In certain embodiments, the linker comprises an aminophenylboronic acid (APBA) group (e.g., 3-aminophenylboronic acid). In certain embodiments, the linker is in the form of -C(=O)NH-(C 6 H 4 )-B(O-) 2 In certain embodiments, the linker is -C(=O)NH-(C 6 H 4 )-B(O-) 2 .

[0227] In certain embodiments, the linker comprises a carboxyphenylboronic acid (CPBA) group (e.g., 4-carboxyphenylboronic acid). In certain embodiments, the linker is in the form of -NHC(=O)-(C 6 H 4 )-B(O-) 2 In certain embodiments, the linker is -NHC(=O)-(C 6 H 4 )-B(O-) 2 .

[0228] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula Ib1 or Formula Ib2:

[0229]

[0230] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula Ib3 or Formula Ib4:

[0231]

[0232] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula Ic1 or Formula Ic2:

[0233]

[0234] In certain embodiments, the conjugate comprises or consists of Formula Ic3 or Formula Ic4:

[0235]

[0236] In certain embodiments, the conjugate comprises or consists of Formula Ic5 or Formula Ic6:

[0237]

[0238] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula Id1 or Formula Id2:

[0239]

[0240] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula Id3 or Formula Id4:

[0241]

[0242] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula Id5 or Formula Id6:

[0243]

[0244] One skilled in the art will appreciate that a linker that is bound to a targeting moiety at one end also has another end that is bound to the surface of the nanoparticle or partitioned into the nanoparticle.The following examples are illustrative.

[0245] As a non-limiting example, quantum dots can be nanocrystals and have a core-shell structure. For example, quantum dots can include nanocrystals of semiconductor materials (e.g., CdSe) with an additional semiconductor layer (ZnS) on its shell. Quantum dots can have a carboxyl-modified surface and / or coating. For example, QDs can be surface-modified with an acid (e.g., oleic acid or 3-mercaptopropionic acid), or QDs can be coated with a layer of polymer coating (e.g., PEG-COOH) with a carboxyl terminus. Such carboxyl termini can be further functionalized with aminophenylboronic acid (APBA), which can bind to SUT targeting agents (such as sucrose) or GUT targeting agents (such as glucose).

[0246] As a non-limiting example, mesoporous silica nanoparticles can be functionalized with silane molecules, including but not limited to triethoxysilane molecules, such as (3-triethoxysilyl)propyl succinic anhydride (TESP) or 3-aminopropyltriethoxysilane (APTES). The silane molecules can anchor themselves to the surface of the silica nanoparticles (e.g., via the triethoxysilane ends). In certain embodiments, the silane molecules can include C 2-18 (For example, C 2-8 ) of a hydrocarbon chain, wherein one or more carbons are optionally replaced by -O-, -N(R a )- or -S- substitution, where R a H or (C 1 -C 6 ) alkyl, so that hydrocarbon chains can be present on the surface of nanoparticles. The end of the silyl molecule can be a group including but not limited to-COOH, amine, thiol, azide, maleimide or boric acid. Finally, the SUT targeting agent can be connected to the silyl molecule, for example, to form a silyl molecule with a SUT targeting agent end-capping. Similarly, the GUT targeting agent can be connected to the silyl molecule, for example, to form a silyl molecule with a GUT targeting agent end-capping.

[0247] As a non-limiting example, liposomes or lipid nanoparticles can be functionalized by amphipathic phospholipid molecules (e.g., phospholipid-PEG-), wherein the hydrophobic lipid tail is distributed into the liposome lipid layer or lipid nanoparticles, and the hydrophilic head is present on the surface of the liposome or lipid nanoparticle. The hydrophilic head can include a PEG chain and / or its end can be a group including but not limited to -COOH, amine, thiol, azide, maleimide or boronic acid. Finally, the SUT targeting agent can be connected to the hydrophilic head, such as forming a hydrophilic head capped with a SUT targeting agent. Similarly, the GUT targeting agent can be connected to the hydrophilic head, such as forming a hydrophilic head capped with a GUT targeting agent.

[0248] In certain embodiments, the surface of the nanoparticles (e.g., carbon dots) in the conjugates comprising the conjugates of Formula I as described herein is further functionalized with one or more cyclodextrin molecular baskets, wherein the cargo can be loaded into the molecular baskets (see Example 1, FIG. 1; or see Example 2, FIG. 14). In certain embodiments, the nanoparticles in the conjugates comprising the conjugates of Formula I as described herein are further functionalized with one or more cyclodextrin molecular baskets via linkers as described herein. As a non-limiting example, in certain embodiments, the linker comprises a phenylboronic acid (PBA) group. In certain embodiments, the linker is -(C 6 H 4 )-B(O-) 2The end-capping, wherein the boron oxygen bond can form a bidentate bond with the two hydroxyl groups of the cyclodextrin. In certain embodiments, the linker is -NHC(=O)-(C 6 H 4 )-B(O-) 2 In certain embodiments, the linker is -NHC(=O)-(C 6 H 4 )-B(O-) 2 .

[0249] In certain embodiments, the surface of the nanoparticles (e.g., carbon dots) may have amino groups (—NH 2 ), the amino group can be covalently linked to carboxylphenylboronic acid (CPBA). In certain embodiments, the surface of the nanoparticle (e.g., carbon dots) can have a carboxyl group (-COOH) that can be covalently linked to aminophenylboronic acid (APBA). Such nanoparticles can be further dually functionalized via boronic acid groups using cyclodextrin and SUT targeting agents (e.g., sucrose) to form SUT targeting agents and cyclodextrin-coated nanoparticles (e.g., see Figures 1 and 6B). Such nanoparticles can be dually functionalized via boronic acid groups using cyclodextrin and GUT targeting agents (e.g., glucose) to form GUT targeting agents and cyclodextrin-coated nanoparticles (e.g., see Figure 14). In certain embodiments, the cargo can be loaded into the cyclodextrin.

[0250] In certain embodiments, the dual-functionalized NP surface may be coated with "n" copies of a SUT targeting agent as described above (e.g., sucrose) and "m" copies of a molecular basket (MB). In certain embodiments, the dual-functionalized NP surface may be coated with "n" copies of a GUT targeting agent as described above (e.g., glucose) and "m" copies of a molecular basket (MB). In certain embodiments, the functionalized NP surface may be coated with "n" copies of SUT and GUT targeting agents as described above and "m" copies of a molecular basket (MB). In certain embodiments, the cargo is loaded into the MB. Depending on the NP size and the surface functionalization reaction, the number of copies of the MB present on the NP surface may vary. In certain embodiments, "m" is about 1, 10, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 70, 71, 72, 73, 74, 75 2 , 10 3 , 10 4 , 10 5 , 10 6 In certain embodiments, "m" is about 1 to 10 6 , 1 to 10 5 , 1 to 10 4 , 1 to 10 3 , 1 to 10 2or 1 to 10. In certain embodiments, "m" is about 1 to 100 or 1000 to 10,000.

[0251] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula le:

[0252] (MB—Connector) m —NP—(Connector—TA) n

[0253] (Formula Ie)

[0254] Wherein: MB is a molecular basket; NP is a nanoparticle; TA is a sucrose transporter (SUT) targeting agent or a glucose transporter (GUT) targeting agent; each linker is independently selected from a linker having a molecular weight of about 20 Daltons to about 20,000 Daltons; m is an integer ≥ 1; and n is an integer ≥ 1. In certain embodiments, TA is a SUT targeting agent. In certain embodiments, TA is a GUT targeting agent. In certain embodiments, the conjugate comprises a mixture of SUT and GUT targeting agents.

[0255] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula 1e1 or Formula 1e2:

[0256]

[0257] In certain embodiments, the conjugate of Formula Ie1 or Formula Ie2 comprises a sucrose structure according to Formula Ic1, Formula Ic2, Formula Id1, or Formula Id2.

[0258] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula 1e3 or Formula 1e4:

[0259]

[0260] In certain embodiments, the conjugate of Formula Ie3 or Formula Ie4 comprises a glucose structure according to Formula Ic3, Formula Ic4, Formula Id3, or Formula Id4.

[0261] In certain embodiments, the conjugate of Formula I, Formula II or Formula III as described herein (e.g., TA and / or linker in Formula I, Formula II or Formula III) comprises a TA and / or linker as shown in the figure (e.g., Figure 14b or Fig.19 )'s glucose and / or linker structure.

[0262] In certain embodiments, a conjugate as described herein comprises a conjugate of formula (I), a cargo, and optionally one or more molecular baskets, wherein the cargo is associated with the nanoparticle and / or the molecular basket. In certain other embodiments, a conjugate as described herein comprises a conjugate of formula (I) but does not comprise a cargo.

[0263] The cargo associated with (e.g., loaded in) the nanoparticles and / or molecular baskets can be released from the nanoparticles or molecular baskets. For example, in certain embodiments, once the cargo loaded in the porous silica nanoparticles or lipid nanoparticles is delivered to the plant / fungus or to the desired site of action (e.g., phloem, stems, and / or roots), the cargo can be released in a sustained manner over time (via diffusion and / or degradation of the NPs).

[0264] Linkers as described above or as described herein can be used in the conjugates described herein (e.g., conjugates of Formula I, Formula II, or Formula III), for example, a targeting agent can be linked to a cargo, a nanoparticle, and / or a molecular basket, or a nanoparticle can be linked to a molecular basket.

[0265] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula II:

[0266] Cargo-Connector-TA(II)

[0267] Wherein: TA is a sucrose transporter (SUT) targeting agent or a glucose transporter (GUT) targeting agent; and the linker has a molecular weight of about 20 Daltons to about 20,000 Daltons. In certain embodiments, TA is a SUT targeting agent. In certain embodiments, TA is a GUT targeting agent. In certain embodiments, the conjugate comprises a mixture of SUT and GUT targeting agents.

[0268] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula IIa:

[0269] Cargo—Linker—Sucrose (Formula IIa).

[0270] In certain embodiments, one end of the linker comprises a boronic acid group that binds to a SUT targeting agent (eg, a disaccharide such as sucrose).

[0271] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula IIa':

[0272] Cargo—Linker—Glucose (Formula IIa').

[0273] In certain embodiments, one end of the linker comprises a boronic acid group that binds to a GUT targeting agent (eg, a monosaccharide such as glucose).

[0274] In certain embodiments, the linker comprises a phenylboronic acid (PBA) group. In certain embodiments, the linker is -(C 6 H 4 )-B(O-) 2 End-capping.

[0275] In certain embodiments, the linker comprises an aminophenylboronic acid group. In certain embodiments, the linker is -C(=O)NH-(C 6 H 4 )-B(O-) 2 In certain embodiments, the linker is -C(=O)NH-(C 6 H 4 )-B(O-) 2 .

[0276] In certain embodiments, the linker comprises a carboxyphenylboronic acid (CPBA) group. In certain embodiments, the linker is -NHC(=O)-(C 6 H 4 )-B(O-) 2 In certain embodiments, the linker is -NHC(=O)-(C 6 H 4 )-B(O-) 2 .

[0277] In certain embodiments, the linker is a cleavable linker (e.g., comprising an ester bond, a disulfide bond, a peptide amide bond, or other bond that is easily cleaved or hydrolyzed with or without enzymatic catalysis). For example, the linked cargo and SUT targeting agent can be separated within the plant / fungus (e.g., in a plant / fungus tissue or cell) or at a desired site of action (e.g., phloem, stem, and / or root). For example, the conjugate can be degraded within the phloem, stem, and / or root, releasing the cargo, NP, and / or molecular basket from the previously linked SUT targeting agent.

[0278] In certain embodiments, the linked cargo and GUT targeting agent can be separated within the fungus. For example, the conjugate can be degraded within the fungus, releasing the cargo, NP and / or molecular basket from the previously linked GUT targeting agent.

[0279] In certain embodiments, the conjugates described herein comprise or consist of a conjugate of Formula IIb1 or Formula IIb2:

[0280]

[0281] In certain embodiments, the conjugates described herein comprise or consist of a conjugate of Formula IIb3 or Formula IIb4:

[0282]

[0283] In certain embodiments, the conjugates described herein comprise or consist of a conjugate of Formula IIc1 or Formula IIc2:

[0284]

[0285] In certain embodiments, the conjugates described herein comprise or consist of a conjugate of Formula IIc3 or Formula IIc4:

[0286]

[0287] In certain embodiments, the conjugates described herein comprise or consist of a conjugate of Formula IIc5 or Formula IIc6:

[0288]

[0289] In certain embodiments, the conjugates described herein comprise or consist of a conjugate of Formula IId1 or Formula IId2:

[0290]

[0291] In certain embodiments, the conjugates described herein comprise or consist of a conjugate of Formula IId3 or Formula IId4:

[0292]

[0293] In certain embodiments, the conjugates described herein comprise or consist of a conjugate of Formula IId5 or Formula IId6:

[0294]

[0295] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula III:

[0296] MB—(Connector—TA) n (III)

[0297] wherein: MB is a molecular basket; and TA is a sucrose transporter (SUT) targeting agent or a glucose transporter (GUT) targeting agent; the linker has a molecular weight of about 20 Daltons to about 20,000 Daltons; and n is an integer ≥ 1. In certain embodiments, TA is a SUT targeting agent. In certain embodiments, TA is a GUT targeting agent. In certain embodiments, the conjugate comprises a mixture of SUT and GUT targeting agents.

[0298] In certain embodiments, exemplary cyclodextrins with functional groups (e.g., amino, carboxyl, or thiol) for functionalization with linkers-targeting agents include, but are not limited to, hexa-(6-amino-6-deoxy)-α-cyclodextrin, hexa-(6-deoxy-6-thiol)-α-cyclodextrin, succinyl-β-cyclodextrin, mono-(6-ethylenediamine-6-deoxy)-β-cyclodextrin, heptath-(6-ethylenediamine-6-deoxy)-β-cyclodextrin, mono-(6-thiol-6-deoxy)-β-cyclodextrin, heptath-(6-deoxy-6-thiol)-β-cyclodextrin, or octa-(6-deoxy-6-thiol)-γ-cyclodextrin. As described herein, one or more targeting agents may each be independently attached to a molecular basket. Thus, in certain embodiments, n is 1, 2, 3, 4, 5, 6, 7, or greater. In certain embodiments, n is about 1 to 8, 1 to 7, 1 to 6, or 1 to 3. In certain embodiments, n is 1, 6, 7, or 8.

[0299] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula IIIa:

[0300] MB—(Linker—Sucrose) n (IIIa).

[0301] In certain embodiments, the conjugate comprises or consists of a conjugate of Formula IIIa':

[0302] MB—(Linker—Glucose) n (IIIa').

[0303] In certain embodiments, the conjugates described herein comprise nanoparticles (e.g., carbon dots) and cyclodextrin molecular baskets. For example, nanoparticles can be covalently linked to cyclodextrins. Thus, SUT targeting agents can be linked to nanoparticles and / or cyclodextrins, and cargo can be loaded into nanoparticles and / or cyclodextrins. Similarly, GUT targeting agents can be linked to nanoparticles and / or cyclodextrins, and cargo can be loaded into nanoparticles and / or cyclodextrins. Thus, in certain embodiments, the conjugates as described herein comprise a conjugate of formula (III), cargo, and optionally nanoparticles, wherein cargo is associated with nanoparticles and / or molecular baskets. In certain other embodiments, the conjugates as described herein comprise a conjugate of formula (III) but do not comprise cargo.

[0304] Certain embodiments of the invention provide compositions comprising a conjugate as described herein.

[0305] The conjugates as described herein can be formulated into suitable dosage forms for plant or fungal application / introduction.

[0306] Common agrochemical and / or nanomaterial formulations are known in the art and include liquid and solid formulations. Exemplary formulations include gels, aqueous or oil-based solutions, dispersions, suspensions or emulsions, such as those described in U.S. Pat. Nos. 5,139,152; 6,403,529; 6,878,674; 7,094,831; 7,109,267 and 9,706,771.

[0307] In certain embodiments, the conjugate may be present in a liquid formulation that can be applied or sprayed onto plants or fungi using, for example, ground / aerial spraying.

[0308] In certain embodiments, the conjugate may be formulated as a pill or tablet formulation. Such formulations may be capable of rapid disintegration in water with minimal or no agitation while providing a fine dispersion of the active ingredient (see, e.g., U.S. Pat. Nos. 5,180,587 and 7,550,156).

[0309] In certain embodiments, the composition comprises an agriculturally acceptable additive or excipient. Suitable additives or excipients that may be present in the formulation include organic solvents, solubilizers, emulsifiers, surfactants, dispersants, preservatives, colorants, fillers, diluents, adhesives, glidants, lubricants, disintegrants, anti-adherents, adsorbents, coating agents, wetting agents, penetrants and carriers. U.S. Patent No. 6,602,823 and the above-mentioned U.S. Patents describe well-known additives, excipients and agricultural chemical formulations.

[0310] In certain embodiments, the compositions described herein include a surfactant. In certain embodiments, the surfactant is a nonionic surfactant (e.g., an organosilicon surfactant Silwet, such as Silwet L-77). In certain embodiments, the surfactant can improve the diffusion of the composition (e.g., a liquid composition) on the surface of the leaf and / or can promote the absorption of the conjugate described herein across the leaf body. In certain embodiments, the surfactant can promote absorption into the stomatal pores of the leaf and / or increase the permeability of the epidermis of the leaf, for example, by partially removing the cuticle.

[0311] In certain embodiments, the composition is in powder dosage form.

[0312] In certain embodiments, the composition (eg, comprising nanoparticles) is in lyophilized form and can be readily reconstituted into liquid form prior to use.

[0313] While the formulation may optionally contain excipients of free sugar molecules (e.g., for osmotic pressure regulation or for cryoprotection in lyophilized formulations), one skilled in the art will appreciate that such free-flowing sugar solutes dissolved in a liquid are themselves free to move / diffuse and are not attached to or co-localized with the cargo, NPs and / or molecular baskets and are therefore not part of a conjugate as described herein.

[0314] method

[0315] The methods described herein can be used to improve the delivery of certain exogenous materials (e.g., a cargo described herein) to the phloem, stem, and / or roots of a plant and / or a fungus or a specific tissue or compartment of a fungus.

[0316] Certain embodiments of the present invention provide a method of introducing a conjugate into a plant in need thereof, the method comprising contacting the plant with a conjugate (e.g., a conjugate described herein) comprising a cargo, nanoparticle and / or cyclodextrin molecular basket linked to a SUT targeting agent. In certain embodiments, such plants contain pests or pathogens (e.g., fungi).

[0317] Those skilled in the art will appreciate that the fungal growth phase begins with conidia or spores, which are dormant (inactive) phases. During this phase, no absorption of nutrients (such as glucose or sucrose) is observed. When exposed to food or plants, the conidia or spores begin to germinate and produce hyphae (active phase). The hyphae proliferate and absorb nutrients, such as glucose or sucrose. Once the food source does not exist and / or environmental conditions are unfavorable, the fungus will enter a dormant phase by producing conidia or spores. The conjugate can be contacted with the plant and / or fungus during germination, after germination, during proliferation, when the fungus forms hyphae, or when spores are formed.

[0318] Certain embodiments of the present invention also provide a method of introducing a conjugate into a fungus in need, the method comprising contacting the fungus with a conjugate (e.g., a conjugate described herein), the conjugate comprising a cargo, a nanoparticle and / or a cyclodextrin molecular basket attached to a SUT targeting agent. Certain embodiments of the present invention also provide a method of introducing a conjugate into a fungus in need, the method comprising contacting the fungus with a conjugate (e.g., a conjugate described herein), the conjugate comprising a cargo, a nanoparticle and / or a cyclodextrin molecular basket attached to a GUT targeting agent. In certain embodiments, the fungus is directly contacted with the conjugate. In certain embodiments, the fungus is contacted with the conjugate by introducing the conjugate into a plant containing the fungus. For example, the fungus can be contacted with the conjugate by introducing the conjugate into the leaves, stems, fruits and / or roots of the plant (e.g., foliar application as described herein, e.g., foliar topical delivery as shown in Examples 1, 2 or 4, or spraying a composition containing the conjugate onto the leaves).

[0319] In certain embodiments, the conjugate comprises a SUT targeting agent linked to a cargo.

[0320] In certain embodiments, the cargo is selected from the group consisting of pesticides, herbicides, and fertilizers (eg, a pesticide, herbicide, or fertilizer described herein).

[0321] In certain embodiments, the conjugate comprises a GUT targeting agent linked to a cargo (eg, a fungicide).

[0322] In certain embodiments, the conjugate comprises or consists of a conjugate of formula (II).

[0323] In certain embodiments, the conjugate comprises a SUT targeting agent attached to a nanoparticle. In certain embodiments, the conjugate comprises a GUT targeting agent attached to a nanoparticle. In certain embodiments, the cargo is associated with the nanoparticle. In certain embodiments, the cargo is not associated with the nanoparticle.

[0324] In certain embodiments, the conjugate comprises or consists of a conjugate of formula (I), which optionally comprises a cargo. In certain embodiments, the conjugate comprising or consisting of a conjugate of formula (I) does not comprise a cargo. In certain embodiments, the conjugate comprising or consisting of a conjugate of formula (I) comprises a cargo. For example, the cargo may be associated with a nanoparticle (e.g., loaded inside). In certain embodiments, the conjugate comprising the conjugate of formula (I) is a multifunctionalized nanoparticle (e.g., a dual-functionalized NP), which comprises one or more SUT targeting agents (e.g., sucrose) and one or more molecular baskets connected to the NP, wherein the cargo is loaded in the molecular basket. In certain embodiments, the conjugate comprising the conjugate of formula (I) is a multifunctionalized nanoparticle (e.g., a dual-functionalized NP), which comprises one or more GUT targeting agents (e.g., glucose) and one or more molecular baskets connected to the NP, wherein the cargo is loaded in the molecular basket.

[0325] In certain embodiments, the conjugate comprises a SUT targeting agent attached to a cyclodextrin molecular basket. In certain embodiments, the conjugate comprises a GUT targeting agent attached to a cyclodextrin molecular basket. In certain embodiments, the cargo is associated with the molecular basket. In certain embodiments, the cargo is not associated with the molecular basket.

[0326] In certain embodiments, the conjugate comprises or consists of a conjugate of formula (III), which optionally comprises a cargo. In certain embodiments, the conjugate comprising or consisting of a conjugate of formula (III) does not comprise a cargo. In certain embodiments, the conjugate comprising or consisting of a conjugate of formula (III) comprises a cargo.

[0327] In certain embodiments, the conjugate is a conjugate as described herein.

[0328] Certain embodiments of the invention provide a method of treating a plant in need thereof (e.g., including a pest or pathogen, such as a fungus), the method comprising contacting the plant with an effective amount of a conjugate as described herein. For example, certain embodiments of the invention provide a method of treating a plant in need thereof, wherein the plant has a phloem pathogen or a root pathogen, the method comprising contacting the plant with an effective amount of a conjugate as described herein.

[0329] In certain embodiments, contacting a plant comprises contacting a leaf of the plant. In certain embodiments, contacting a plant comprises contacting the top surface of a leaf of the plant.

[0330] In certain embodiments, after contacting, the delivered conjugate is more enriched in the phloem veins of the leaf compared to a control material not linked to the SUT targeting agent.

[0331] For example, in certain embodiments, following contacting, the delivered cargo is more enriched in the phloem veins of the leaf compared to cargo not linked to the SUT targeting agent.

[0332] In certain embodiments, upon contacting, the delivered nanoparticles are more enriched in the phloem veins of the leaf compared to nanoparticles not linked to the SUT targeting agent.

[0333] In certain embodiments, after contacting, the delivered cyclodextrin molecular basket is more enriched in the phloem veins of the leaf compared to cyclodextrin molecular baskets not linked to the SUT targeting agent.

[0334] In certain embodiments, the delivered conjugate (e.g., cargo, NP and / or molecular basket) is at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 100%, at least about 200%, at least about 300%, at least about 400%, at least about 500%, at least about 600% or more more enriched in the phloem veins of the leaves compared to a control (e.g., an equivalent or corresponding material not linked to a SUT targeting agent). Methods for detecting or measuring delivered materials are known in the art and described herein (e.g., fluorescence imaging, liquid chromatography-based methods such as HPLC and / or LC-MS). For example, the assays described herein (see Example 1) can be used.

[0335] In certain embodiments, the delivered conjugate is more efficiently delivered into the stem and / or root of the plant compared to a control material not linked to the SUT targeting agent.

[0336] For example, in certain embodiments, upon contacting, the delivered cargo is more efficiently delivered into the stem and / or root of the plant compared to a cargo not linked to a SUT targeting agent.

[0337] In certain embodiments, upon contacting, the delivered nanoparticles are more efficiently delivered into the stem and / or root of the plant compared to nanoparticles not linked to a SUT targeting agent.

[0338] In certain embodiments, upon contacting, the delivered cyclodextrin molecular basket is more efficiently delivered into the stem and / or root of the plant compared to a cyclodextrin molecular basket not linked to a SUT targeting agent.

[0339] In certain embodiments, the delivered conjugate (e.g., cargo, NP and / or molecular basket) is delivered to the stem and / or root of a plant at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 100%, at least about 200%, at least about 300%, at least about 400%, at least about 500%, at least about 600%, or more, more efficiently than a control (e.g., an equivalent or corresponding material not linked to a SUT targeting agent).

[0340] In certain embodiments, a conjugate described herein is delivered to the phloem veins of the leaf within 60 min, 50 min, 40 min, 30 min, 20 min, 10 min, 5 min, 4 min, 3 min, 2 min, or 1 min (e.g., within 40 or 30 min) after the leaf is contacted with the conjugate.

[0341] In certain embodiments, the delivered conjugate is more enriched in the phloem veins of leaves and / or is more efficiently delivered to the stems and / or roots of the plant at about 30 min, 40 min, 50 min, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, 16 hr, 20 hr, 24 hr or longer after the plant is contacted with the conjugate (e.g., topically applied to the leaves), as described herein, compared to a control material not linked to a SUT targeting agent.

[0342] In certain embodiments, at least about 40%, 45%, 50%, 55%, 60%, 65%, or 70% of the phloem-loaded conjugates described herein are delivered to the roots of the plant. For example, at least about 50%, 60%, or 70% of the phloem-loaded conjugates (i.e., conjugates that enter the leaf phloem veins after contact with the leaf surface) ultimately reach the roots of the plant.

[0343] In certain embodiments, the methods described herein allow for the delivery of certain exogenous materials (e.g., cargoes described herein) to the phloem, stems, and / or roots of a plant without contacting the soil surrounding the plant roots. Thus, in certain embodiments, the methods do not include contacting the soil surrounding the plant with the conjugate.

[0344] In certain embodiments, the plant is a plant selected from the group consisting of wheat, oats, corn, rice, barley, vegetables (e.g., lettuce, broccoli, carrots, spinach, or peppers), fruit plants (e.g., apples, oranges, pears, grapes, or peaches), nut trees (e.g., almonds, walnuts, or pecans), or plants providing fiber material (e.g., cotton).

[0345] In certain embodiments, the plant is a weed.

[0346] In certain embodiments, the plant in need suffers from a disease caused by a phloem pathogen. Exemplary microbial phloem pathogens include, but are not limited to, Candidatus Liberibacterasiaticus (citrus greening), Arsenophonus bacteria, Serratia marcescens (cucurbit yellow vine disease), Candidatus Phytoplasma asteris (Aster Yellows Witches' Broom), and Spiroplasma kunkeli.

[0347] In certain embodiments, a plant in need thereof suffers from a disease caused by a root pathogen (eg, Ralstonia solanacearum or a pathogen that invades and / or colonizes plant roots).

[0348] In certain embodiments, a plant in need thereof is infected with a fungus (eg, a fungus described herein, such as a fungus expressing SUT or GUT).

[0349] Certain embodiments of the invention provide a method of introducing a conjugate as described herein (eg, a conjugate comprising a glucose transporter (GUT) targeting agent linked to a cargo) into a fungus, comprising contacting the fungus with the conjugate.

[0350] In certain embodiments, the conjugate is more efficiently delivered into the fungus (eg, enhanced intracellular delivery into the fungus) compared to a control material not linked to the GUT targeting agent.

[0351] In certain embodiments, the delivered conjugate is more enriched within the fungus compared to a control material not linked to a GUT targeting agent.

[0352] For example, in certain embodiments, the delivered cargo is more enriched within the fungus compared to a cargo not linked to a GUT targeting agent.

[0353] In certain embodiments, the delivered nanoparticles are more enriched within the fungus compared to nanoparticles not linked to a GUT targeting agent.

[0354] In certain embodiments, the delivered cyclodextrin molecular basket is more enriched within the fungus than a cyclodextrin molecular basket not linked to a GUT targeting agent.

[0355] In certain embodiments, the delivered conjugate (e.g., cargo, NP and / or molecular basket) is more enriched in the fungus by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 100%, at least about 200%, at least about 300%, at least about 400%, at least about 500%, at least about 600% or more (e.g., 7, 8, 9, 10, 15 or 20 times or more) compared to a control (e.g., an equivalent or corresponding material not linked to a GUT targeting agent). Methods for detecting or measuring delivered materials are known in the art and described herein (e.g., fluorescence imaging, liquid chromatography-based methods such as HPLC and / or LC-MS). For example, the assays described herein (see Example 2) can be used.

[0356] Certain embodiments of the present invention provide a method of inhibiting fungi, the method comprising contacting the fungi with an effective amount of a conjugate as described herein (e.g., a conjugate comprising a fungicide as described herein). In certain embodiments, the fungi are directly contacted with the conjugate. In certain embodiments, the fungi are contacted with the conjugate by introducing the conjugate into a plant comprising the fungi. As used herein, the term "inhibit" refers to reducing the vitality of the fungi, slowing or stopping the growth of the fungi, and / or eliminating the presence of the fungi.

[0357] Thus, the invention described herein also provides a method of treating a fungal infection in a plant, wherein the method comprises contacting the plant and / or the fungus with a conjugate as described herein.

[0358] In certain embodiments, the leaves, stems, fruits and / or roots of the plant are infected by fungi. In certain embodiments, the leaves of the plant are infected by fungi. In certain embodiments, the stems of the plant are infected by fungi. In certain embodiments, the roots of the plant are infected by fungi. In certain embodiments, the fruit of the plant is infected by fungi.

[0359] In certain embodiments, the methods include contacting the fungus with a conjugate.

[0360] In certain embodiments, the method includes contacting the plant with the conjugate. One or more organs / positions of the plant can be contacted with the conjugate. In certain embodiments, the method includes contacting the blades of the plant with the conjugate (e.g., topical application, such as spraying or depositing the conjugate or composition on the blade). In certain embodiments, the method includes contacting the stems of the plant with the conjugate (e.g., topical application, such as spraying or depositing the conjugate or composition on the stem). In certain embodiments, the method includes contacting the plant fruit of the plant with the conjugate (e.g., topical application, such as spraying or depositing the conjugate or composition on the fruit). In certain embodiments, the method includes contacting the root of the plant with the conjugate. In certain embodiments, when the roots of the plant near the ground or underground are infected by fungi, contacting the plant may include contacting the soil around the plant or the root.

[0361] In certain embodiments, the fungus is a fungus selected from the group consisting of Psoralea oryzae, certain species of Botrytis (e.g., Botrytis cinerea), certain species of Puccinia spp., Fusarium graminearum, Fusarium oxysporum, Bleucophylla brunnerii, Mycosphaeria graminearum, certain species of Colletotrichum anthracis, Ustilago maydis, Puccinia flax, and Psoralea tritici.

[0362] In certain embodiments, the fungus is a fungus selected from the group consisting of certain species of Alternaria, certain species of Bipolaris, certain species of Botrytis, certain species of Cochliobolus, certain species of Colletotrichum, certain species of Erysiphe, certain species of Endocronartium, certain species of Fusarium, certain species of Glomerella, certain species of Phragmidium, and certain species of Puccinia.

[0363] In certain embodiments, the fungus is a Botrytis cinerea fungus.

[0364] In certain embodiments, the plant is suffering from a fungal infection selected from the group consisting of gray mold, anthracnose, leaf blight, leaf spot, leaf rust, gall rust, wilt, early blight, and powdery mildew.

[0365] In certain embodiments, a conjugate as described herein comprising an appropriate active ingredient cargo (e.g., a cargo as described herein) is useful for controlling the causative agents of the following illustrative plant diseases: certain species of Albugo (white rust), which are on ornamentals, vegetables (e.g., A. candida), and sunflower (e.g., A. tragopogonis); certain species of Alternaria (alternaria leaf spot), which are on vegetables (e.g., A. dauci or A. porri), rapeseed (A. brassicicola or A. brassicae), sugar beet (A. truncatula), enuis), fruit (e.g., A. grandis), rice, soybean, potato and tomato (e.g., A. solani, A. grandis or A. alternata), tomato (e.g., A. solani or A. alternata) and wheat (e.g., A. triticina); certain species of Aphanomyces on sugar beets and vegetables; certain species of Ascochyta on cereals and vegetables, e.g., A. tritici (anthracnose) on wheat and A. hordei on barley; Aureobasidium zeae (Aureobasidium zeae) on corn and vegetables. zeae) (synonym Kapatiella zeae) on corn; certain species of the genera Bipolaris and Drechslera (sexual form: certain species of Cochliobolus), such as corn leaf spot (D. maydis) or corn leaf spot (B. zeicola) on corn, such as spotted blight (B. sorokiniana) on cereals and such as B. oryzae on rice and lawns; B. graminis (formerly Erysiphe graminis) (powdery mildew) on cereals (e.g. wheat or barley); Botryotinia cinerea (sexual form: Botryotinia cinerea) on corn. fuckeliana): gray mold on fruits and berries (e.g. strawberries), vegetables (e.g. lettuce, carrots, celery, and cabbage); B. squamosa or B.allii (on the onion family), oilseed rape, ornamentals (e.g. Be eliptica ), grapevines, forest plants and wheat; Bremia lactucae (downy mildew) on lettuce; Ceratocystis (synonym Ophiostoma) species (rots or wilts) on broadleaf and evergreen trees, e.g. C. ulmi (Dutch elm disease) on elms; Cercospora species (cercospora leaf spot) on maize (e.g. gray leaf spot: C. zeae-ma ydis), rice, sugar beet (e.g., C. beticola), sugar cane, vegetables, coffee, soybean (e.g., C. sojina or C. kikuchii), and rice; certain species of Cladobotryum (synonym Dactylium) (e.g., C. mycophilum (formerly Dactylium) dendroides (sexual forms: Nectria albertinii, Nectria rosella (synonym: Hypomyces rosellus) on mushrooms; certain species of Cladosporium on tomatoes (e.g., C. fulvum: leaf mold) and cereals, e.g., C. herbarum (smut) on wheat; Claviceps purpurea (ergot) on cereals; Helminthosporium (sexual forms: Helminthosporium ofBipolaris)) on corn (C. carbonum), cereals (e.g. C. sativus, anamorph: (C. oryzae)) and rice (e.g. C. miyabeanus, anamorph: C. oryzae); certain species of Colletotrichum (tetramorph: Colletotrichum) ((anthracnose), on cotton (e.g. gossypii), corn (e.g. C. graminicola: anthracnose stalk rot), soft fruit, potato (e.g. C. coccodes: black spot), legumes (e.g. C. lindemuthianum), soybeans (e.g. C. truncatum or C. gloeosporioides), vegetables (e.g. C.lagenarium or C. capsici), fruit (e.g. C. acutatum), coffee (e.g. C. coffeanum or C. kahawae), and C. gloeosporioides on various crops; certain species of Corticium, such as C. sasakii (shear blight), on rice; Corynespora spp. cassiicola) (leaf spot) on soybeans, cotton and ornamentals; certain species of Cycloconium, such as C. oleaginum, on olive trees; certain species of Cylindrocarpon (e.g., fruit canker or young vine decline, teleomorphs: Nectria or certain species of Neonectria) on fruit trees, grapevines (e.g., C. liriodendri, teleomorph: Neonectria liriodendri: blackleg) and ornamentals; Dematophora necatrix (telemorph: Rosellininia necatrix) (root and stem rot) on soybean; certain species of Diaporthe, such as D. phaseolorum (damping-off) on soybean; certain species of Pyrenophora (synonym Helminthosporium, teleomorph: Pyrenophora) on corn, cereals such as barley (e.g., D. teres, net blotch) and wheat (e.g., D. tritici-repentis: brown spot), rice, and turf; Esca (wilt, dry blight) on grapevines, by Formitiporia punctata (synonym Phellinus punctata), F.mediterranea), Phaeomoniella chlamydospora (formerly Phaeoacremonium chlamydosporum), Phaeoacremonium aleophilum, and / or Botryosphaeria obtusa; Elsinoe species on pome fruit (E. pyri), soft fruit (E. veneta: anthracnose), and grapevines (E. ampelina: anthracnose); Entyloma oryzae (leaf smut) on rice; Epicoccum species (black mold) on wheat; Erysiphe species (powdery mildew) on rice; mildew), on sugar beet (E. betae), vegetables (e.g. E. pisi), such as cucurbits (e.g. E. cichoracearum), cabbage, rapeseed (e.g. E. cruciferarum); Eutypa lata (Eutypa canker or wilt, anamorph: Cytosporinalata, synonym Libertella blepharis) on fruit trees, grapevines and ornamental trees; certain species of the genus Helminthosporium (synonym Helminthosporium) on corn (e.g. E. turcicum); certain species of the genus Fusarium (teleomorph: Gibberella) (wilt, root rot or stem rot) on various plants, such as F. graminearum or F. culmorum (root rot, spot or head blight) on cereals (e.g. such as wheat or barley), F. oxysporum, which on tomatoes, F. solani (now synonymous with F. sp. glycines, F. virguliforme), and F. tucumaniae and F. brasiliense, each of which causes soybean sudden death syndrome, and F.verticillioides, which is on corn; Gaeumannomyces graminis (take-all disease), which is on cereals (e.g., wheat or barley) and corn; certain species of Gibberella, which are on cereals (e.g., G. zeae) and rice (e.g., G. fujikuroi: Bakanae disease); Glomerella cingulata, which is on grapevines, pome fruits, and other plants, and G. gossypii, which is on cotton; Grainstaining complex, which is on rice; Guignardia spp., which is on rice; bidwellii (black rot), on grapevines; Gymnosporangium species, on rosaceae and junipers, e.g., G. sabinae (pear rust), on pears; Helminthosporium species (synonym Entomophthora, teleomorph: Helicoverpa), on corn, corn, tomatoes, and rice; Hemileia species, e.g., H. vaportrix (coffee leaf rust), on coffee; Isariopsis clavispora (synonym Cladosporium vitis), on grapevines; Macrophomina phaseolina (synonym phaseoli) (root and stem rot), on soybeans and cotton; Microdochium nivale) (synonym Fusarium nivale) (pink snow mold) on cereals (e.g. wheat or barley); Microsphaera diffusa (powdery mildew) on soybeans; certain species of Monilinia, such as M. laxa, M. fructicola and M. fructigena (synonym Monilia: blossom end and branch end, brown rot) on stone fruits and other Rosaceae plants; certain species of Mycosphaerella, which are on cereals, bananas, soft fruits and peanuts, such as, for example, M. graminicola (asexual form: Septoria graminicola, formerly Septoria tricitici: leaf blight) on wheat or M. fijiensis (M.fijiensis (synonym Pseudocercospora fijiensis: black leaf spot) and M. musicola, which grows on bananas, M. arachidicola (synonym M. arachidis or Cercospora arachidis), Berkeley Mycosphaeria (M. berkeleyi on peanuts, M. pisi on peas, and M. brassiciola on Brassicas; Peronospora species (downy mildew) on cabbage (e.g., P. brassicae), rapeseed (e.g., P. parasitica), onion (e.g., P. destructor), tobacco (P. tabacina), and soybean (e.g., P. manshurica); Phakopsora pachyrhizi and P. meibomiae (soybean rust, which is on soybean; certain species of Phialophora, for example on grapevines (e.g. P. tracheiphila and P. tetraspora) and soybeans (e.g. P. gregata: stem rot); Phoma lingam (synonyms Leptosphaeria biglobosa and L. maculans: root and stem rot), which is on rapeseed and cabbage, P. betae (root rot, leaf spot and damping-off), which is on sugar beets, and P. zeae-maydis (synonyms Phyllostica zeae) on corn; Phomopsis species on sunflower, grapevines (e.g. P. viticola: can and leaf spot) and soybeans (e.g. stem rot: P. phaseoli, teleomorph: Diaporthe phaseolorum); Physoderma maydis (brown spot) on corn; Phytophthora species (blight rot, root rot, leaf rot, fruit rot and stem rot) on various plants such as red peppers and cucurbits (e.g. P. capsici), soybeans (e.g. P. sojae), and soybeans (e.g. P.megasperma, synonym P. sojae), potato and tomato (e.g. P. infestans: late blight) and broadleaf trees (e.g. P. ramorum: sudden oak death); Plasmodiophora brassicae (clubroot), on cabbage, rape, radish and other plants; certain species of Plasmopara, such as (P. viticola) (downy mildew of grapes), on grapevines and P. halstedii, on sunflowers; certain species of Podosphaera (powdery mildew), on rosaceae, hops, pome and soft fruit (e.g. P. leucotricha, on apples) and cucurbits (P. xanthii); certain species of Polymyxa, for example on cereals such as wheat and barley (P. graminis) and sugar beets (P. betae) and thereby transmit viral diseases; Pseudocercosporella herpotrichoides) (synonyms: Oculimacula yallundae, O. acuformis: eyespot, teleomorph: Tapesia yallundae) on cereals, such as wheat or barley; Pseudoperonospora (downy mildew) on various plants, such as P. cubensis on cucurbits or P. humili on hops; Pseudopezicula tracheiphila (red fire or 'rotbrenner', anamorph: Phialophora) on grapevines; certain Puccinia species species (rusts), on various plants, for example P. triticina (brown or leaf rust), P. striiformis (stripe or yellow rust), P. hordei (dwarf rust), P. graminis (stem rot or black rust) or P. recondita (brown or leaf rust), on cereals, such as, for example, wheat, barley or rye, P. kuehnii (orange rust), on sugarcane and P. asparagus (P.asparagi, on asparagus; certain species of the genus Pyrenopeziza, such as P. brassicae, on rapeseed; Pyrenophoratritici-repentis (asexual form: Drechslera tritici-repentis) (brown spot), on wheat or P. teres (net spot), on barley; certain species of the genus Pyricularia, such as P. oryzae (sexual form: Magnaporthe grisea: rice blast) on rice and P. grisea on turf and cereals; certain species of Pythium (damping-off) on turf, rice, corn, wheat, cotton, rapeseed, sunflower, soybean, sugar beet, vegetables and various other plants (e.g. P. ultimum or P. aphanidermatum and P. oligandrum on mushrooms; certain species of Ramularia, such as R. collo-cygni (R. collo-cygni leaf spot, physiological leaf spot) on barley, R. leucophylla (R. leucophylla leaf spot, R. leucophylla leaf spot) on barley, .areola) (teleological form: Mycosphaerellaareola) on cotton and R.beticola on sugar beet; certain species of Rhizoctonia on cotton, rice, potato, turf, corn, rapeseed, potato, sugar beet, vegetables and various other plants, such as R.solani (root and stem rot) on soybean, R.solani (shear blight) on rice or R.cerealis (rhizoctonia spring leaf blight) on wheat or barley; Rhizopus stolonifer (Rhizopus stolonifer) on cotton, rice, potato, turf, corn, rapeseed, potato, sugar beet, vegetables and various other plants, such as R.solani (root and stem rot) on soybean, R.solani (shear blight) on rice or R.cerealis (rhizoctonia spring leaf blight) on wheat or barley; stolonifer (black mold, soft rot) on strawberries, carrots, cabbage, grapevines and tomatoes; Rhynchosporium secalis and R. commune (scorch) on barley, rye and triticale; Sarocladium oryzae and S. attenuatum (sheath rot) on rice; Sclerotinia species (stem rot or white mold) on vegetables (S. minor and S. sclerotiorum) and field crops such as rapeseed, sunflower (e.g. S.sclerotiorum) on soybeans, S. rolfsii (synonym Athelia rolfsii) on soybeans, peanuts, vegetables, corn, cereals and ornamentals; certain species of Septoria on various plants, such as S. glycines (brown spot) on soybeans, S. tritici (synonym Triticum triticum, leaf blight) on wheat, and S. nodorum (synonym Stagonospora nodorum) Stagonosporablotch on cereals; Uncinula necator (synonym Erysiphenecator) (powdery mildew, anamorph: Oidium tuckeri) on grapevines; Setosphaeria species (big blight) on corn (e.g., S. turcicum, synonym Helminthosporium turcicum) and turf; Sphacelotheca species (smut) on corn (e.g., S. reiliana, synonym Ustilagoreiliana: head smut), sorghum, and sugarcane; Sphaerotheca fuliginea (synonym Podosphaera xanthii: powdery mildew) on cucurbits; Spongosphaeria subterranea (powdery scab) on potatoes; scab), which is on tomatoes and thus spreads viral diseases; certain species of Stagonospora, which are on cereals, for example S. nodorum (Stagonospora blotch, teleomorph: Leptosphaeria nodorum [syn. Phaeosphaeria nodorum] syn. Septoria nodorum), which is on wheat; Synchytrium endobioticum, which is on potatoes (potato cancer); certain species of Taphrina, for example T. deformans (leaf curl), which is on peaches and T.pruni) (plum sac fruit disease) on plums; certain species of Thielaviopsis (black root rot) on tobacco, pome fruit, vegetables, soybeans and cotton, for example, T. basicola (synonym Chalara elegans); certain species of Tilletia (common smut or bunt) on cereals, such as, for example, T. tritici (synonym T. caries, wheat bunt) and T. controversy smut on wheat; certain species of Trichoderma harzianum (Trichoderma harzianum) (common smut or bunt) on cereals, such as, for example, T. tritici (synonym T. caries, wheat bunt) and T. controversy smut on wheat; harzianum on mushrooms; Typhula incarnata (grey snow mold) on wheat or barley; certain species of Urocystis, such as U. occulta (stalk smut), on rye; certain species of Uromyces (rusts) on vegetables such as legumes (e.g. U. appendiculatus, synonym U. phaseoli), sugar beets (e.g. U. betae or U. beticola) and on dry beans (e.g. U. vignae, U. pisi, U. viciae-fabae and U. fabae); Ustilago species (loose smut) on cereals (e.g. U. nuda and U. avaenae), corn (e.g. U. maydis: corn smut) and sugar cane; Venturia species (black scab) on apples (e.g. V. inaequalis) and pears; and Verticillium species (wilt) on various plants such as fruits and oats, grapevines, soft fruits, vegetables and field crops, e.g. V. longisporum on rapeseed, V. dahliae on strawberries, rapeseed, potatoes and tomatoes, and V. fungicola on mushrooms; Z. tritici on cereals. .

[0366] In certain embodiments, the conjugates as described herein, comprising an appropriate active ingredient cargo (e.g., a cargo described herein), are useful for controlling the causative agents of the following illustrative plant diseases: rusts on soybeans and cereals (e.g., Puccinia pachyrhizi and Puccinia gracilis on soybeans; Puccinia tritici and Puccinia striatum on wheat); mildews on specialty crops, soybeans, rapeseed, and sunflowers (e.g., Botrytis cinerea on strawberries and grapevines, Sclerotinia sclerotiorum, Sclerotinia microspores, and Sclerotinia sclerotiorum on rapeseed, sunflower, and soybeans); fusarium diseases on cereals (e.g., Fusarium culmorum and Fusarium graminearum on wheat); downy mildews on specialty crops (e.g., Plasmopara spp. on grapevines, Phytophthora infestans, and Phytophthora spp. on wheat); infestans, which is on tomatoes); powdery mildews on specialty crops and cereals (e.g., Uncinaria vitis, which is on grape vines, certain species of Powdery Mildew spp., which are on various specialty crops, and Blumeria brucei, which is on cereals); and leaf spots on cereals, soybeans, and corn (e.g., Septoria tritici and Septoria glumae, which are on cereals, Septoria soybean, which is on soybeans, and certain species of Cercospora, which are on corn and soybeans).

[0367] The terms "introduce" and "introduction" refer to contacting a plant or fungus, or a part thereof, with a material (e.g., a conjugate described herein). For example, a conjugate or a composition comprising a conjugate can be applied to a plant or fungus, or a part thereof (e.g., a leaf or spore). In certain embodiments, a plant or fungus, or a part thereof (e.g., leaves and / or other tissues) is sprayed with a conjugate or a composition comprising a conjugate. In certain embodiments, a plant or fungus, or a part thereof (e.g., leaves dipped in a composition) is coated with a conjugate or a composition comprising a conjugate. In certain embodiments, a conjugate or a composition comprising a conjugate is applied to a plant or fungus (e.g., via injection).

[0368] The terms "treat" and "treatment" refer to both therapeutic treatment and prophylactic or preventative measures, wherein the objective is to prevent or reduce an undesirable change, disorder or disease in a plant. For purposes of the present invention, beneficial or desired results include, but are not limited to, alleviation of symptoms, reduction in disease severity, a stable (i.e., non-worsening) disease state, a delay or slowing of disease progression or spread, and an improvement in the disease state, whether detectable or undetectable. Plants in need of treatment include plants already suffering from a disorder or disease, as well as those susceptible to a disorder or disease, or those to be prevented from a disorder or disease.

[0369] The phrase "therapeutically effective amount" means an amount of a conjugate as described herein that (i) treats a particular disease, disorder or condition, (ii) reduces, ameliorates or eliminates one or more symptoms of a particular disease, disorder or condition, or (iii) prevents or delays the onset of one or more symptoms of a particular disease, disorder or condition described herein. The phrase "effective amount" may also mean an amount effective to inhibit pests and / or pathogens.

[0370] Unless otherwise indicated, the term "alkyl" by itself or as part of another substituent means a radical having the specified number of carbon atoms (i.e., C 1-8 Examples include (C 1 -C 8 ) alkyl, (C 2 -C 8 ) alkyl, (C 1 -C 6 ) alkyl, (C 2 -C 6 ) alkyl and (C 3 -C 6 Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, and higher homologs and isomers.

[0371] As used herein, the term "aryl" refers to a single all-carbon aromatic ring or a multiple fused all-carbon ring system in which at least one ring is aromatic. For example, in certain embodiments, the aryl group has 6 to 20 carbon atoms, 6 to 14 carbon atoms, 6 to 12 carbon atoms, or 6 to 10 carbon atoms. Aryl includes phenyl. Aryl also includes multiple fused carbocyclic ring systems (e.g., ring systems comprising 2, 3 or 4 rings) with about 9 to 20 carbon atoms, wherein at least one ring is aromatic and wherein other rings may be aromatic or not aromatic (i.e., cycloalkyl). When valence requirements allow, the rings of the multiple fused ring systems may be connected to each other via fusion, spiral and bridge bonds. It should be understood that, as defined above, the connection point of the multiple fused ring system may be at any position in the ring system, including the aromatic portion or carbocyclic portion of the ring. Non-limiting examples of aryl include, but are not limited to, phenyl, indenyl, indanyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, anthracenyl, etc.

[0372] As used herein, the term "heteroaryl" refers to a single aromatic ring having at least one atom other than carbon in the ring, wherein the atom is selected from the group consisting of oxygen, nitrogen and sulfur; "heteroaryl" also includes multiple fused ring systems having at least one such aromatic ring, which multiple fused ring systems will be further described below. Thus, "heteroaryl" includes a single aromatic ring of about 1 to 6 carbon atoms and about 1-4 heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur. Sulfur and nitrogen atoms may also exist in oxidized form, provided that the ring is aromatic. Exemplary heteroaryl ring systems include, but are not limited to, pyridyl, pyrimidinyl, oxazolyl or furanyl. "Heteroaryl" also includes multiple fused ring systems (e.g., ring systems comprising 2, 3 or 4 rings) in which the heteroaryl as defined above is condensed with one or more rings selected from cycloalkyl, aryl, heterocycle and heteroaryl. It will be appreciated that the point of attachment of the heteroaryl or heteroaryl multiple fused ring system may be at any suitable atom of the heteroaryl or heteroaryl multiple fused ring system, including carbon atoms and heteroatoms (e.g., nitrogen). Exemplary heteroaryl groups include, but are not limited to, pyridyl, pyrrolyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrazolyl, thienyl, indolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, furanyl, oxadiazolyl, thiadiazolyl, quinolyl, isoquinolyl, benzothiazolyl, benzoxazolyl, indazolyl, quinoxalinyl, and quinazolinyl.

[0373] The term "halo" or "halogen" refers to bromo, chloro, fluoro, or iodo. In some embodiments, halogen refers to chloro or fluoro.

[0374] The stereochemical definitions and conventions used herein generally follow SP Parker, ed., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York; and Eliel, E and Wilen, S., "Stereochemistry of Organic Compounds", John Wiley & Sons, Inc., New York, 1994. The compounds of the present invention may contain asymmetric centers or chiral centers and therefore exist in different stereoisomeric forms. It is intended that all stereoisomeric forms of the compounds of the present invention (including but not limited to diastereomers, enantiomers and atropisomers) and mixtures thereof (such as racemic mixtures) form part of the present invention. Many organic compounds exist in optically active forms, that is, they have the ability to rotate the plane of plane polarized light. When describing optically active compounds, the prefixes D and L or R and S are used to indicate the absolute configuration of the molecule about its chiral center. The prefixes d and l or (+) and (-) are used to specify the sign of the rotation of the compound to plane polarized light, (-) or 1 means that the compound is left-handed. Compounds with (+) or d prefixes are dextrorotatory. For a given chemical structure, these stereoisomers are identical except that they are mirror images of each other. Specific stereoisomers may also be referred to as enantiomers, and mixtures of such isomers are often referred to as enantiomeric mixtures. A 50:50 mixture of enantiomers is referred to as a racemic mixture or racemate, which may occur in a chemical reaction or process without stereoselectivity or stereospecificity. The terms "racemic mixture" and "racemate" refer to an equimolar mixture of two enantiomeric species without optical activity.

[0375] Those skilled in the art will appreciate that certain compounds described herein having chiral centers may exist and be separated in optically active and racemic forms. Some compounds may exhibit polymorphism. It should be understood that the present invention encompasses any racemic, optically active, polymorphic or stereoisomeric forms or mixtures thereof of compounds of the present invention having the useful properties described herein, and how to prepare optically active forms is well known in the art (e.g., by resolving racemic forms using recrystallization techniques, by synthesis from optically active starting materials, by chiral synthesis, or by chromatographic separation using chiral stationary phases).

[0376] When a bond in a compound formula herein is drawn in a nonstereochemical fashion (eg, planar), the atoms to which the bond is attached include all stereochemical possibilities.

[0377] Certain embodiments of the present invention are as follows:

[0378] Embodiment 1. A conjugate comprising a sucrose transporter (SUT) targeting agent linked to a cargo, wherein the conjugate is capable of being delivered to a plant or fungus, and wherein the cargo is an agent capable of producing a desired effect in the plant or fungus upon delivery of the conjugate to the plant or fungus.

[0379] Embodiment 2. The conjugate of embodiment 1, wherein the cargo is a pesticide, a herbicide, or a fertilizer.

[0380] Embodiment 3. The conjugate of embodiment 1 or 2, further comprising nanoparticles and / or molecular baskets, wherein the nanoparticles are selected from the group consisting of quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, metal or metal oxide nanoparticles, and macro- or micronutrient-based nanoparticles.

[0381] Embodiment 4. The conjugate of embodiment 3, comprising nanoparticles linked to one or more SUT targeting agents.

[0382] Embodiment 5. The conjugate of embodiment 3 or 4, wherein the cargo is associated with the nanoparticle or with the molecular basket.

[0383] Embodiment 6. The conjugate of embodiment 5, wherein the cargo is associated with the nanoparticle.

[0384] Embodiment 7. The conjugate of embodiment 5, wherein the cargo is associated with the molecular basket.

[0385] Embodiment 8. The conjugate of any one of Embodiments 3 to 7, wherein the molecular basket comprises beta cyclodextrin.

[0386] Embodiment 9. The conjugate of embodiment 8, wherein the cargo forms an inclusion complex with the cyclodextrin.

[0387] Embodiment 10. The conjugate of embodiment 9, wherein the cargo is selected from the group consisting of chlorpyrifos, methyl viologen, oxyfluorfen, imazaquin, norfloxacin, chloroform, penoxsulam, norfloxacin, and trifluorfen, trifluorfen, fluazifop, pyraclostrobin, and boscalid.

[0388] Embodiment 11. The conjugate of any one of embodiments 3 to 6, comprising a conjugate of formula I:

[0389] NP—(Connector—TA) n (I)

[0390] wherein: NP is the nanoparticle; TA is the sucrose transporter (SUT) targeting agent; the linker has a molecular weight of about 20 Daltons to about 20,000 Daltons; and n is an integer ≥1.

[0391] Embodiment 12. The conjugate of embodiment 11, wherein the NP is further functionalized with one or more molecular baskets.

[0392] Embodiment 13. The conjugate of embodiment 12, wherein the molecular basket comprises β-cyclodextrin.

[0393] Embodiment 14. The conjugate of embodiment 12 or 13, wherein the cargo is associated with the molecular basket.

[0394] Embodiment 15. The conjugate of embodiment 13, wherein the cargo forms an inclusion complex with the cyclodextrin.

[0395] Embodiment 16. The conjugate of any one of embodiments 12 to 15, wherein the cargo is selected from the group consisting of chlorpyrifos, methyl viologen, oxyfluorfen, imazaquin, norfloxacin, chloroform, penoxsulam, norfloxacin, trifluoperazine, fluazifop, pyraclostrobin, boscalid and acifluorfen.

[0396] Embodiment 17. The conjugate according to embodiment 1, which is a conjugate of formula II:

[0397] Cargo-Connector-TA(II)

[0398] wherein: TA is the sucrose transporter (SUT) targeting agent; and the linker has a molecular weight of about 20 Daltons to about 20,000 Daltons.

[0399] Embodiment 18. The conjugate of any one of embodiments 7 to 10, comprising a conjugate of formula III:

[0400] MB—(Connector—TA) n (III)

[0401] wherein: MB is the molecular basket; TA is the sucrose transporter targeting agent (SUT) targeting agent; the linker has a molecular weight of about 20 Daltons to about 20,000 Daltons; and n is an integer ≥1.

[0402] Embodiment 19. The conjugate of any one of Embodiments 11 to 18, wherein the linker has a molecular weight of about 20 Daltons to about 5,000 Daltons.

[0403] Embodiment 20. The conjugate of any one of embodiments 11 to 18, wherein the linker has a molecular weight of about 20 Daltons to about 1,000 Daltons.

[0404] Embodiment 21. The conjugate of any one of embodiments 11 to 20, wherein the linker comprises a boronic acid group -B(O-) 2 , where each O- is bonded to TA.

[0405] Embodiment 22. The conjugate of any one of embodiments 11 to 21, wherein the linker has the structure -XYZ-; wherein:

[0406] X is a bond, -O-, -S-, -C(=O)-, -N(R a )-, -C(=O)NH-, -C(=S)NH-, -C(=O)O-, -C(=O)S-, -NHSO 2 -, -OC(=O)NH-, -NHC(=O)NH-, -NHC(=S)NH-, -Si(R b ) 3 or -B(R c ) 2 ,

[0407] Z is a bond, -O-, -S-, -C(=O)-, -N(R a )-, -C(=O)NH-, -C(=S)NH-, -C(=O)O-, -C(=O)S-, -NHSO 2 -, -OC(=O)NH-, -NHC(=O)NH-, -NHC(=S)NH-, -Si(R b ) 3 , or -B(R c ) 2 ;

[0408] R a H or (C 1 -C 6 )alkyl;

[0409] Each R b are independently O-, -OH or (C 1- C 4 ) alkoxy;

[0410] Each R c is O- connected to TA;

[0411] Y is a divalent, saturated or unsaturated, branched or unbranched chain (C 2- C 18 ) hydrocarbon chain, wherein one or more carbons of the hydrocarbon chain are optionally replaced by -O-, -N(Rs )-, -S-, aryl (e.g., -C 6 H 4 -) or heteroaryl, and wherein the hydrocarbon chain is optionally substituted on carbon by one or more substituents selected from the group consisting of halo, hydroxy, thiol, oxo (=O) and thioxo (=S); and

[0412] R s H or (C 1 -C 6 )alkyl.

[0413] Embodiment 23. The conjugate of embodiment 22, wherein Z is -B(R c ) 2 .

[0414] Embodiment 24. The conjugate of any one of embodiments 1 to 23, wherein the sucrose transporter (SUT) targeting agent is a saccharide.

[0415] Embodiment 25. The conjugate of any one of embodiments 1 to 23, wherein the sucrose transporter (SUT) targeting agent is sucrose.

[0416] Embodiment 26. The conjugate of embodiment 11, comprising formula Ic1 or formula Ic2:

[0417]

[0418] Embodiment 27. The conjugate of embodiment 12, comprising a conjugate of formula Ie:

[0419] (MB—Connector) m —NP—(Connector—TA) n

[0420] (Formula Ie)

[0421] wherein: MB is the molecular basket; NP is the nanoparticle; TA is the sucrose transporter (SUT) targeting agent; each linker is independently selected from linkers having a molecular weight of about 20 Daltons to about 20,000 Daltons; m is an integer ≥1; and n is an integer ≥1.

[0422] Embodiment 28. The conjugate of embodiment 27, comprising formula Ie1 or formula Ie2:

[0423]

[0424] Embodiment 29. The conjugate of any one of embodiments 3 to 28, wherein the nanoparticles are carbon dots, carbon nanotubes, silica nanoparticles, metal or metal oxide nanoparticles, lipid nanoparticles, liposomes, or macro- or micronutrient-based nanoparticles.

[0425] Embodiment 30. The conjugate of any one of embodiments 3 to 28, wherein the nanoparticles have a diameter of about 1 nm to 300 nm.

[0426] Embodiment 31. The conjugate of any one of Embodiments 3 to 28, wherein the nanoparticles have a diameter of about 1 nm to 50 nm.

[0427] Embodiment 32. The conjugate of any one of embodiments 1 to 31, wherein the cargo is a herbicide or a pesticide.

[0428] Embodiment 33. The conjugate of any one of embodiments 1 to 32, wherein the cargo has a molecular weight of less than 1000 g / mol.

[0429] Embodiment 34. A method of introducing a conjugate into a plant or fungus expressing a sucrose transporter (SUT), the method comprising: contacting the plant or fungus with the conjugate of any one of embodiments 1 to 33.

[0430] Embodiment 35. The method of embodiment 34, comprising contacting a fungus with the conjugate.

[0431] Embodiment 36. The method of embodiment 34, comprising contacting a plant with the conjugate.

[0432] Embodiment 37. The method of embodiment 36, wherein the plant comprises leaves contacted with the conjugate.

[0433] Embodiment 38. The method of any one of embodiments 34 to 37, wherein the conjugate is contacted with the plant and / or fungus during germination, after germination, during proliferation, when the fungus is forming hyphae, or when spores are formed.

[0434] Embodiment 39. The method of any one of Embodiments 36 to 38, wherein the plant suffers from a disease caused by a phloem pathogen.

[0435] Embodiment 40. The conjugate of any one of embodiments 36 to 38, wherein the plant suffers from a disease caused by a root pathogen.

[0436] Embodiment 41. The method of any one of Embodiments 36 to 38, wherein the plant is a weed.

[0437] Embodiment 42. A method for delivering a conjugate to a plant or fungus, comprising contacting the plant or fungus with a conjugate comprising nanoparticles and / or molecular baskets linked to a sucrose transporter (SUT) targeting agent, wherein the nanoparticles are selected from the group consisting of quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, metal or metal oxide nanoparticles, and macro- or micronutrient-based nanoparticles.

[0438] Embodiment 43. The method of embodiment 42, wherein the conjugate is contacted with the plant and / or fungus during germination, after germination, during proliferation, when the fungus is forming hyphae, or when spores are formed.

[0439] Embodiment 44. A conjugate comprising a sucrose transporter (SUT) targeting agent attached to a nanoparticle, wherein the conjugate is capable of being delivered to a plant or fungus, and the nanoparticle is selected from the group consisting of: quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, metal or metal oxide nanoparticles, and macro- or micronutrient-based nanoparticles.

[0440] Embodiment 45. The conjugate of embodiment 44, comprising a conjugate of formula I:

[0441] NP—(Connector—TA) n (I)

[0442] Wherein: NP is a nanoparticle selected from the group consisting of: quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, metal or metal oxide nanoparticles, and macro- or micronutrient-based nanoparticles; TA is the sucrose transporter (SUT) targeting agent; the linker has a molecular weight of about 20 Daltons to about 20,000 Daltons; and n is an integer ≥1.

[0443] Embodiment 46. A conjugate as described in embodiment 45, wherein the nanoparticles are selected from carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, and macro- or micronutrient-based nanoparticles.

[0444] Embodiment 47. The conjugate of any one of Embodiments 44 to 46, which does not comprise a cargo.

[0445] Embodiment 48. The conjugate of any one of Embodiments 44 to 46, comprising a cargo.

[0446] Embodiment 49. A method comprising detecting the conjugate of any one of embodiments 44 to 48 in a plant or fungus.

[0447] The invention will now be illustrated by the following non-limiting examples.

[0448] Example 1: Targeted delivery of nanomaterials to phloem via plant biorecognition

[0449] Current practices for delivering agrochemicals are inefficient, with only a portion reaching the intended target of the plant. In this article, nanomaterials functionalized with sucrose can be delivered to the plant phloem faster and more efficiently through the foliage, which is a vascular tissue that transports sugars, agrochemicals, and signaling molecules. The high affinity of sucrose molecules to sucrose transport membrane proteins (SUT) on phloem companion cells mediates the biorecognition and loading of quantum dots (sucQD) functionalized with sucrose. The QD fluorescence optical properties can measure the rapid absorption and translocation (<40min) of sucQDs in the phloem of wheat leaves by fluorescence microscopy. The foliage delivery of engineered nanomaterials by plant biorecognition molecules provides a method for guiding agrochemicals to specific plant organs with enhanced absorption efficiency.

[0450] introduction

[0451] Rapid population growth has led to increasing global demands on agricultural productivity, requiring significant increases in food production 1 Agricultural practices create some of the most significant pressures on Earth’s natural resources, leading to deforestation, groundwater contamination, and increased greenhouse gas emissions. 2,3 The runoff of agricultural chemicals (such as pesticides and fertilizers) from farmland is one of the most negative impacts on the environment and human health. 4 Pesticides are the main type of agricultural chemicals that accumulate in the environment and can be transferred into the food chain through progressive biomagnification. 5 Although the use of pesticides improves the yield and quality of crops, excessive use of pesticides leads to the development of pesticide resistance in agricultural pests (i.e., pathogens), affects air quality, and pollutes water and soil. 6 This is particularly concerning because it is estimated that of the 5.6 billion pounds of pesticides applied worldwide, less than 0.1% achieve their intended biological targets. 8-9 .

[0452] New methods for improving the efficiency of agrochemical delivery require the development of new technologies 10,11,12Plant phloem provides a functional transport system to deliver materials directly from leaves to other plant organs, including underground roots, without interacting with the complex and diverse soil matrix. 13 In addition, plant vascular systems harbor destructive plant pathogens that undermine crop yields. 14 The long-distance transport of organic compounds such as amino acids and photosynthates (i.e., sugars) in the phloem is driven by the pressure of bulk flow between cells within companion cells and in sieve tube vascular elements, which coordinate the loading and unloading of phloem sap. 15-17 Sucrose is the major sugar transported in plant phloem. Plant transport of sucrose is highly regulated and requires the H+-coupled sucrose uptake transporter (SUT). 15,17 We show here that these intrinsic mechanisms for sucrose recognition and transport through the phloem provide untapped opportunities for directing nanomaterial and agrochemical cargoes via plant biorecognition.

[0453] Nanomaterials with tunable physical and chemical properties are emerging tools for improving the delivery efficiency of chemical and biomolecular cargoes in plants. For example, the size and charge of a nanomaterial can play a role in its foliar delivery efficiency to plant cells and organelles, including stomatal guard cells and chloroplasts. 18 Recently, it has been demonstrated that engineered nanomaterials can be guided by targeting peptide motifs that target chemical cargoes to photosynthetic organelles. 19 , or can be targeted to stomata and trichomes with a protein coating 20 Methods for targeting nanomaterials to the phloem using plant molecular mechanisms have not been explored. Current methods for delivering chemicals to the phloem rely on conjugation to antibodies, which are not suitable for agricultural applications due to their high cost and stability issues under ambient conditions. 21-23 Herein, an alternative approach was discovered for surface functionalization of nanoparticles using biorecognition molecules with affinity for SUT (eg, sucrose) that is scalable and inexpensive.

[0454] Quantum dots (QDs) are traceable model nanoparticles that enable the evaluation of interactions with plant biointerfaces using a variety of advanced analytical tools. The intrinsic and bright non-photobleaching fluorescence of QDs with tunable emission wavelength can be imaged in plants with high spatial and temporal resolution by confocal fluorescence microscopy. 19 Furthermore, the tunable surface chemistry of QDs allows for coating with biorecognition motifs for targeted delivery to plant tissues, cells, and organelles. 24 . Taken together, quantum dots are a valuable tool for tracking and quantifying the targeted delivery of nanomaterials in plants to fundamentally understand nanoparticle-plant interactions.

[0455] This example evaluates how functionalizing the surface of nanoparticles (e.g., QDs) with sucrose affects foliar delivery and absorption of nanoparticles into the phloem of wheat (Triticum aestivum) plants. It is hypothesized that the delivery of sucrose-coated QDs (sucQDs) to the phloem can be improved by biorecognition of plants ( FIG. 1 ). High spatial and temporal resolution confocal microscopy was performed to determine the distribution of QDs in plant leaves. The translocation of QDs into the leaf vascular system was assessed by epifluorescence microscopy. For example, absorption and transport of QDs out of leaves were shown by confocal imaging studies. This example provides a method for targeting nanomaterials to the phloem to study the interaction of nanoparticles with plants, plant biology, and the implementation of nano-enabled agriculture.

[0456] result

[0457] Functionalization of nanoparticles for targeted delivery to phloem

[0458] QDs and CDs were functionalized with sucrose to enable biorecognition by phloem SUT. Sucrose was coated on the QD surface (sucQD) or CD surface (suc-β-CD) through the strong binding between the boronic acid groups and the carbohydrates (i.e., sucrose) containing the same coplanar hydroxyl groups (Figure 1b). 19 . We functionalized CDs with β-cyclodextrin molecular baskets to demonstrate the potential of β-cyclodextrin molecular baskets as nanocarriers for targeted delivery of agrochemicals to plants (Figure 1b). Transmission electron microscopy (TEM) images showed that the average sizes of sucQDs and suc-β-CDs were approximately 5.0±0.8nm and 9.1±2.8nm, respectively (Figure 2a). The hydrodynamic diameters (in 10mM TES pH 7.4) of sucQDs (17.6±1.4nm) and suc-β-CDs (18.1±5.8nm) were similar (Figure 2b). Both sucQDs and QDs are negatively charged, with high zeta potentials of -45.9±7.4mV and -57.1±2.5mV, respectively (10mM TES, pH7.0). Suc-β-CD and core CD showed lower negative charge zeta potentials than QDs, at -31.1 ± 1.1 mV and -28.9 ± 7.7 mV, respectively (Figure 2c). The size and charge of the nanoparticles may play a role in their distribution in plant cells or organelles. 13,18. The DLS sizes and zeta potentials of these nanomaterials are within the range reported to promote internalization through leaf biological surface barriers, including plant cell walls and plasma membranes. Although sucQDs exhibited the same characteristic absorption peak as QDs at 575 nm (Figure 2d), the normalized absorbance of sucQDs increased slightly in the UV range, which was attributed to the sucrose molecules introduced on its surface. The absorption spectrum of suc-β-CD showed that the absorption of CD in the UV and visible ranges was broadened due to the introduction of sucrose molecules and β-cyclodextrin. One of the significant properties of these nanomaterials is their high, tunable and stable fluorescence, which allows tracking the translocation and distribution of nanomaterials within leaf tissues and cells. As shown in Figure 2e, the surface coating on QDs had no significant effect on the intrinsic emission fluorescence properties of sucQDs, with a maximum emission peak at 580 nm. For suc-β-CD, the CD fluorescence was blue-shifted from 520 nm to 486 nm by surface coating. The fluorescence of sucQD and suc-β-CD avoided optical interference with the autofluorescence of leaves (above about 620 nm) (Figure 2e). 18,19 We measured Fourier transform infrared (FT-IR) spectra to confirm the functionalization of QDs and CDs with sucrose and / or β-cyclodextrin (Figure 2f–g). sucQD or suc-β-CD showed the characteristic vibration mode of amide II (1590 cm-1 for sucQD). -1 And suc-B-CD is 1600cm -1 ), CH bending of sucrose or β-cyclodextrin molecules (1459 cm -1 , 1413cm -1 ), BO stretching of sucQD and suc-β-CD (1326 cm -1 、1330cm -1 ), and sucrose at 1047cm -1 CO stretching at 1101, 1060, 1014 cm -1 Taken together, these results indicate that both QDs and CDs have been successfully functionalized with sucrose or β-cyclodextrin molecules and that the remarkable optical properties of these nanomaterials are maintained.

[0459] The colloidal stability of nanomaterials in simulated phloem sap was investigated to determine the effects on QD aggregation and degradation of nanoparticles through dissolution of nanoparticle elements. 25 By including the reported sugar and metal ion contents ( Fig.12) to simulate phloem sap, and the changes in the characteristic absorbance peak of QDs at 574 nm were measured after 1 and 7 days of incubation with simulated phloem sap. QDs and sucQDs showed negligible peak shift or changes in absorbance intensity (Figure 2f). There was no change in the hydrodynamic diameter under simulated phloem sap conditions ( Fig.13 ). Overall, these results show high stability with no aggregation or degradation over a week, which is longer than the experiments in this example.

[0460] Nanoparticle uptake in plant vascular systems

[0461] How sucrose surface coating of QDs affects the translocation of nanoparticles from the leaf surface into the phloem was investigated by high spatial resolution (206-233 nm xy and 2 μm z-axis resolution) confocal fluorescence microscopy imaging (Figure 3). The nanoparticles were delivered to the adaxial (top) leaf surface of 5 μl sucQDs or QDs in a buffer (10 mM TES) with 0.1 wt % Silwet surfactant by foliar application. QDs were imaged by confocal microscopy in the loading area where the nanoparticles were topically applied on the wheat leaf surface for 30 min (Figure 3a). These exposure conditions at a QD concentration of 200 μM had no significant effect on leaf health as determined by photosynthesis assays. CO2 emissions of leaves exposed to QDs and sucQDs at different light levels 2 The assimilation rate (A) was similar to that of the control without nanoparticles ( Figure 8 ). After 30 min of exposure, unmodified QDs were distributed throughout the leaf tissue. In contrast, sucQDs were primarily localized to the main veins of the leaves, indicating absorption into the vascular system (Figure 3a). To examine the distribution of CDs in leaves, suc-β-CD and uncoated CDs were applied to the leaf surface and imaged by confocal fluorescence microscopy. suc-β-CD also showed fluorescent signals arranged in a linear pattern, indicating localization in the leaf vascular system (Figure 3c). To determine the vascular tissue that transports sucQDs, co-localization analysis of sucQDs with phloem labeled with fluorescent dyes was performed. 5,6-Carboxyfluorescein diacetate (CFDA) is converted into the fluorescent form carboxyfluorescein (CF) when it reacts with cellular esterases after penetration into the phloem tissue. 26 This technique is used for in vivo imaging of phloem companion cells and sieve tube molecules in plants 26 CF fluorescence emission was imaged in a region that did not overlap with QD fluorescence (<550 nm, Fig. 9 ). The CFDA dye translocated from the leaf surface into the phloem in a similar manner as QDs ( FIG. 10A ). The colocalization of sucQD fluorescence with the CF dye (87±5.5%) indicated that sucQDs translocated through leaf phloem tissue.

[0462] Real-time imaging of nanoparticle translocation in the phloem

[0463] To investigate the translocation dynamics of QDs in the phloem, an epifluorescence microscope was customized to detect changes in nanoparticle fluorescence intensity in the leaf vasculature in planta (see Methods, Figure 4a). Changes in QD fluorescence intensity were monitored in real time downstream of the foliar application area (towards the stem) in leaves of intact living plants (Figure 4b). Phloem sap in mature leaves is transported toward the stem, while xylem sap moves in the opposite direction. During 40 min, the sucQD fluorescence intensity downstream of the foliar application area doubled, demonstrating the translocation of the nanoparticles through the phloem vascular tissue (Figure 4c). In contrast, the fluorescence intensity of unmodified QDs increased only 1.25 times the initial intensity over the same time frame. Merged bright-field images of the leaf vasculature with QD fluorescence illustrate the localization of the nanoparticles in the phloem after 40 min of exposure (Figure 4d, Fig.11 The rapid translocation of QDs in the phloem is within the expected time range for phloem sap velocities of 0.05 to 0.2 mm / s. 27,28 The QD fluorescence signals in stomatal guard cells on the leaf surface indicated the stomatal uptake pathway into the leaf tissue and vascular system. Taken together, these results suggest that sucQDs can be rapidly taken up and translocated through the leaf phloem.

[0464] Biorecognition-mediated uptake of nanoparticles into phloem

[0465] To understand the biorecognition mechanism that directs sucQD into the phloem, the translocation kinetics of sucQD and glucose-coated QDs (gluQD) were examined. We hypothesized that the SUT (sucrose transporter) membrane protein that facilitates sucrose loading into the phloem increases the binding affinity of sucQD to this plant vascular tissue. 29,30 SUT transports sucrose and other sugars in plants; however, the specificity for sucrose is much higher than for glucose. The hydrodynamic size and charge of gluQD are similar to those of sucQD ( Fig.13 ). However, the translocation kinetics of gluQD were slower and resulted in a 1.25-fold increase in fluorescence intensity in the leaf phloem (Figure 4c), similar to that of unmodified QDs, indicating that the glucose moiety was not effective in improving the loading and translocation of QDs into the phloem. To examine the uptake mechanism, the effect of temperature on the change in fluorescence intensity of sucQDs in the phloem was compared (Figure 4e). Endocytosis is an energy-dependent mechanism that is inhibited at low temperatures. 31sucQDs were detected in the phloem after exposure at 25 °C, but not after exposure at 4 °C, suggesting that the transport of sucQDs into phloem vessels may be energy-dependent and may proceed via an endocytic pathway. In contrast, nanoparticle uptake in mesophyll cells of photosynthetic leaves has been reported to be independent of endocytosis. 32,33 . Therefore, an alternative mechanism of nanoparticle lipid bilayer disruption may be involved. Overall, these results suggest that sucQDs are directed to the phloem via SUT recognition of sucrose moieties on the QD surface. Previous studies have also shown that Au nanoparticles (NPs) that more easily enter the phloem are more efficiently translocated out of exposed leaves and that foliar-applied Au NPs (3, 10, and 50 nm) in wheat plants were significantly more efficient than foliar-applied TiO 2 and ZnO NP (25nm) 34 , the root is an important library (sink) 13 .

[0466] discuss

[0467] Coating the surface of nanoparticles with biorecognition molecules is a promising method for targeted delivery of nanomaterials to plant tissues (i.e., phloem). In this article, QDs are used as model traceable nanoparticles, which allow for more efficient delivery of sucrose-coated nanoparticles (e.g., sucQDs) to phloem under the guidance of plant biorecognition. The distribution and translocation of QDs in plant leaves were evaluated by imaging the fluorescence emission of QDs with confocal microscopy and epifluorescence microscopy. SucQDs are highly co-localized with phloem in plant leaves, translocated in the time range of reported sap phloem speeds and in the expected phloem sap direction (towards the stem), indicating that sucQDs are rapidly absorbed by the leaf epidermis and translocated in the phloem by a large amount of sap flow. The sucQD biorecognition in the phloem vessel is mediated by the affinity of the sucrose moiety to SUT, and the absorption into the phloem may be carried out via endocytosis-mediated mechanisms or other alternative mechanisms (such as nanoparticle destruction of the lipid bilayer), which remain to be studied. SucQDs were delivered long distances from exposed mature leaves to roots via the phloem. This biorecognition approach provides a tool for delivering agrochemical cargoes to roots via foliage (e.g., via nanomaterials) while avoiding disturbing interactions with the soil. The sucrose-coated nanomaterials approach can be used to deliver biocompatible and environmentally friendly nanoparticles such as carbon dots with molecular baskets. 19 and mesoporous silica nanoparticles carrying active ingredients 35 , and phytonutrient-based nanoparticles 36,37 ) targeted delivery to the phloem, leading to more efficient and sustainable agriculture with less environmental impact.

[0468] method

[0469] Synthesis of sucrose and β-cyclodextrin coated carbon dots (suc-B-CD). suc-B-CD was synthesized by coating the CD core with β-cyclodextrin and sucrose. The core carbon dots (CD) were synthesized by slight modifications of a previously reported protocol (Hu et al. ACS Nano 2020, 14, 7, 7970-7986). The CD core was synthesized by a hydrothermal reaction using citric acid, urea, and ammonium hydroxide. In brief, 1.92 g citric acid (Fisher, 99.7%) and 2.40 g urea (Fisher, 99.2%) were dissolved in 2 mL DI water, and 1.35 mL ammonium hydroxide (Sigma Aldrich, NH 3 ·H 2 The mixture was reacted at 180 ° C for 1.5 h, cooled to room temperature, and redissolved in DI water. Aggregates were removed by centrifugation at 4,500 rpm for 30 min. The solution was further filtered using a syringe filter (Whatman, pore size 0.02 μm) to remove larger particles. Next, the CD core was functionalized to BA-terminated CD (BA-CD) by carboxyphenylboronic acid (CBA). NHS (75 nmol) and EDC / HCl (75 nmol) were added to the CD in TES buffer (10 mM TES buffer, pH 7.4). Then, the mixture was vortexed (750 rpm) for 15 min at ambient temperature. CBA solution (75 nmol) was added and reacted at room temperature for 3 h. In order to wash off excess CBA, a dialysis membrane (1K MWCO, Spectrum Laboratories) was used and dialyzed with 2 L DI water. To introduce β-cyclodextrin and sucrose onto sucCD, BA-CD was first dispersed in TES buffer (10 mM TES buffer; pH 10.4), then 10 ul of 5 mM β-cyclodextrin was added and stirred overnight. After reacting with β-cyclodextrin, the mixture was washed with a dialysis membrane (1K MWCO, Spectrum Laboratories) by dialyzing with 2 L DI water. Subsequently, sucrose was reacted with β-cyclodextrin by repeating the same protocol.

[0470] Synthesis of sucrose coated QDs (sucQDs). sucQDs were synthesized from carboxylated QDs functionalized with 3-aminophenylboronic acid (APBA) capped QDs (BA-QDs). Carboxylated QDs (QSH-580, Ocean nanotech., USA) were functionalized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) activation reaction. Briefly, NHS (75 nmol) and EDC / HCl (75 nmol) were added to 0.5 uM carboxylated QDs in TES buffer (10 mM TES buffer, pH 7.4). The mixture was then vortexed (750 rpm) for 15 min at ambient temperature. APBA solution (75 nmol) was added to the activated carboxylated QD solution to generate boronic acid functionalized quantum dots (BA-QDs). The reaction was stirred (750 rpm) for 3 h at room temperature. Excess APBA was removed using a centrifugal filter (30K amicon filter, Millipore) with ddH2O, and repeated at least five times. To avoid aggregation during the centrifugation step, BA-QDs were resuspended in the centrifugal filter using a bath sonication step after refilling with ddH2O. To synthesize sucQDs, BA-QDs were suspended in TES buffer (10mMTES buffer; pH 10.4), and then 10ul of 5mM sucrose solution was added to the BA-QD solution and vortexed overnight. Centrifugal filters (30K amicon filters, Millipore) were used in ddH2O. 2 Sucrose-coated BA-QDs (sucQDs) were washed in 10 mM TES (pH 7.5) for plant experiments.

[0471] Characterization of quantum dots. The absorbance, photoluminescence, hydrodynamic size, zeta potential and Fourier transform infrared spectroscopy (FT-IR) of sucQDs and QDs were measured to characterize their physicochemical properties. The hydrodynamic size and zeta potential were determined using a Nano-S Malvern Zetasizer in 10 mM TES buffer (pH 7) in the presence of 0.1 mM NaCl. The UV-visible absorption spectrum was measured in a UV-2600 Shimadzu spectrophotometer to calculate the concentration of sucQDs based on its absorbance at 575 nm. The concentration of sucQDs (mol L -1 ), where Abs is the absorbance, ∈ is the extinction coefficient, L is the thickness of the absorbing medium, and c is the concentration.

[0472] Abs=∈×L×c, (1)

[0473] Transmission electron microscopy (TEM) was performed on a Philips FEI Tecnai 12 microscope with an accelerating voltage of 120 kV. TEM samples were prepared by placing a drop of particle solution on an ultrathin carbon film grid. The surface coating and functional groups on the nanomaterials were characterized by FT-IR (Bruker spectrometer, Alpha I). ​​FT-IR measurements were performed at each step of the sucQD synthesis to analyze the functional groups on the nanoparticle surface.

[0474] Plant growth. Wheat plants (Triticum aestivum, USA) were grown in an F-1200 plant growth chamber (Hipoint, Taiwan, China) at a light intensity of 200 μmol m -2 s -1 Photosynthetically active radiation, day / night temperature of 24 ± 1 ° C and 21 ± 1 ° C, relative humidity of 60%, and day / night photoperiod of 14 / 10 h. Soil was purchased from Planet Natural (Sunshine Mix #1) and autoclaved before use. Each wheat seedling was grown in a separate pot of 2.25 inches square. Plants were watered once every two days with tap water.

[0475] Nanoparticle delivery into leaves. A solution of 10 uL QDs (200 nM) in 10 mM TES buffer (pH 7.4) was topically applied to the abaxial surface of wheat leaf layers for 30 min to allow QDs to translocate into the vascular system. The remaining QD droplets were gently removed by wiping with Kimwipes.

[0476] Confocal fluorescence microscopy of QDs in plant leaves. QDs in wheat leaves were imaged using a TCS SP5 laser scanning confocal microscope (Leica Microsystems, Germany). Leaves were exposed to QDs as explained above. Leaf discs were immediately collected with a cork drill in the loading and tracking zones (10 mm from the loading zone to the stem) and mounted on microscope slides for confocal microscopy imaging of QDs. Leaf discs in microscope slides were placed in chambers made with observation gel (132700, Carolina) containing 0.3 ml of perfluorodecalin (P9900, Sigma-Aldrich) observation solution to improve confocal imaging. The confocal microscope settings were as follows: ×20 and x40 objectives (UAPON-340, 1.15w); QDs were excited by 405 nm laser; z stack slice thickness = 2 μm. The PMT detection range was set as follows: 550–600 nm for QD, 700–800 nm for chloroplast autofluorescence, and 500–550 nm for CDFA. All confocal microscopy images were analyzed using FIJI (ImageJ).

[0477] Epifluorescence microscopy of QD uptake and translocation into phloem. To monitor the translocation of sucQDs into the vascular system in real time, epifluorescence images were collected by a custom-made microscope system. Wheat leaves of intact living plants were mounted on the microscope stage using metal clips. QDs were applied to wheat leaves as described above. Roots and soil in pots were wrapped with aluminum foil to prevent splashing onto the microscope setup. The measurement point on the abaxial plane of the leaf surface was focused at 10 mm from the loading area exposed to sucQDs or QD suspensions. QDs were excited using a fluorescent light source (U-HGLGPS, Oylmpus), and fluorescence emission was imaged using a PMT detector (Retiga R3, Qimaging). Images of QD fluorescence emission or chloroplast autofluorescence were collected using an optical cube filter as follows: for QDs, excitation 405 nm, emission detection range 570-590 nm; for chloroplasts, excitation 405 nm, emission detection range 700-800 nm. The integration time was set to 0.1 s. The collected images were converted to calculate the integrated mean fluorescence intensity using FIJI (ImageJ).

[0478] References cited in Example 1

[0479] 1.Spiertz,J.H.J.&Ewert,F.Crop production and resource use to meet thegrowing demand for food,feed and fuel:opportunities and constraints.NJAS-Wageningen Journal of Life Sciences 56,281-300(2009).

[0480] 2.Dalin,C.&Rodriguez-Iturbe,I.Environmental impacts of food trade viaresource use and greenhouse gas emissions.Environ.Res.Lett.(2016).

[0481] 3.DeFries,R.S.,Rudel,T.,Uriarte,M.&Hansen,M.Deforestation driven byurban population growth and agricultural trade in the twenty-firstcentury.Nat.Geosci.3,178-181(2010).

[0482] 4.Alam,Z.The Use of Biotechnology to Reduce the Dependency of CropPlants on Ferrilizers,Pesticides,and Other Agrochemicals.Biotechnollogy inFunctional Foods and Nutraceuticals 197-218(2010)doi:10.1201 / 9781420087123-c13.

[0483] 5.Sebastian,A.,Nangia,A.&Prasad,M.N.V.Chapter 18-Advances inagrochemical remediation using nanoparticles.in Agrochemicals Detection,Treatment and Remediation (ed.Prasad,M.N.V.)465-485(Butterworth-Heinemann,2020).

[0484] 6.Lamichhane,J.R.,Dachbrodt-Saaydeh,S.,Kudsk,P.&Messéan,A.Toward aReduced Reliance on Conventional Pesticides in European Agriculture.PlantDis.100,10-24(2016).

[0485] 8.Stone,W.W.,Gilliom,R.J.&Ryberg,K.R.Pesticides in U.S.Streams andRivers:Occurrence and Trends during 1992-2011.Environ.Sci.Technol.48,11025-11030(2014).

[0486] 9.Alavanja,M.C.R.Introduction:Pesticides Use and Exposure,ExtensiveWorldwide.Reviews on Environmental Health vol.24(2009).

[0487] 10.Su,Y.et al.Delivery,uptake,fate,and transport of engineerednanoparticles in plants:a critical review and data analysis.Environ.Sci.:Nano6,2311-2331(2019).

[0488] 11.Lowry,G.V.,Avellan,A.&Gilbertson,L.M.Opportunities and challengesfor nanotechnology in the agri-tech revolution.Nat.Nanotechnol.14,517-522(2019).

[0489] 12.Hofmann,T.et al.Technology readiness and overcoming barriers tosustainably implement nanotechnology-enabled plant agriculture.Nature Food 1,416-425(2020).

[0490] 13.Avellan,A.et al.Nanoparticle Size and Coating Chemistry ControlFoliar Uptake Pathways,Translocation,and Leaf-to-Rhizosphere Transport inWheat.ACS Nano(2019)doi:10.1021 / acsnano.8b09781.

[0491] 14.Yadeta,K.A.&J Thomma,B.P.H.The xylem as battleground for planthosts and vascular wilt pathogens.Front.Plant Sci.4,97(2013).

[0492] 15.VAN Bel,A.J.E.&Van Bel,A.J.E.The phloem,a miracle ofingenuity.Plant,Cell&Environment vol.26 125-149(2003).

[0493] 16.Lucas,W.J.et al.The plant vascular system:evolution,developmentand functions.J.Integr.Plant Biol.55,294-388(2013).

[0494] 17.Dinant,S.&Lemoine,R.The phloem pathway:new issues and olddebates.C.R.Biol.333,307-319(2010).

[0495] 18.Hu,P.et al.Nanoparticle Charge and Size Control Foliar DeliveryEfficiency to Plant Cells and OrganellesACS Nano(2020)doi:10.1021 / acsnano.9b09178.

[0496] 19.Santana,I.,Wu,H.,Hu,P.&Giraldo,J.P.Targeted delivery ofnanomaterials with chemical cargoes in plants enabled by a biorecognitionmotif.Nat.Commun.11,2045(2020).

[0497] 20.Spielman-Sun,E.et al.Protein coating composition targetsnanoparticles to leaf stomata and trichomes.Nanoscale(2020)doi:10.1039 / c9nr08100c.

[0498] 21.Gravato-Nobre,M.J.et al.Meloidogyne incognita Surface AntigenEpitopes in Infected Arabidopsis Roots.J.Nematol.31,212-223(1999).

[0499] 22.Kim,J.S.&Daniel,G.Immunolocalization of pectin and hemicelluloseepitopes in the phloem of Norway spruce and Scots pine.Trees 31,1335-1353(2017).

[0500] 23.DeWitt,N.D.&Sussman,M.R.Immunocytological localization of anepitope-tagged plasma membrane proton pump(H(+)-ATPase)in phloem companioncells.Plant Cell 7,2053-2067(1995).

[0501] 24.Koo,Y.et al.Fluorescence Reports Intact Quantum Dot Uptake intoRoots and Translocation to Leaves of Arabidopsis thaliana and SubsequentIngestion by Insect Herbivores.Environ.Sci.Technol.49,626-632(2015).

[0502] 25.Su,Y.et al.Delivery,Fate,and Mobility of Silver Nanoparticles inCitrus Trees.ACS Nano 14,2966-2981(2020).

[0503] 26.Cayla,T.et al.Live imaging of companion cells and sieve elementsin Arabidopsis leaves.PLoS One 10,e0118122(2015).

[0504] 27.Payvandi,S.,Daly,K.R.,Zygalakis,K.C.&Roose,T.Mathematicalmodelling of the Phloem:the importance of dirfusion on sugar transport atosmotic equilibrium.Bull.Math.Biol.76,2834-2865(2014).

[0505] 28.Savage,J.A.,Zwieniecki,M.A.&Holbrook,N.M.Phloem transport velocityvaries over time and among vascular bundles during early cucumber seedlingdevelopment.Plant Physiol.163,1409-1418(2013).

[0506] 29.Reinders,A.Evolution of plant sucrose uptaketransporters.Frontiers in Plant Science vol.3(2012).

[0507] 30.Sun,Y.&Ward,J.M.Arg188 in rice sucrose transporter OsSUT1 iscrucial for substrate transport.BMC Biochemistry vol.13 26(2012).

[0508] 31.Low,P.S.&Chandra,S.Endocytosis in Plants.Annu.Rev.PlantPhysiol.Plant Mol.Biol.45,609-631(1994).

[0509] 32.Wu,H.,Tito,N.&Giraldo,J.P.Anionic Cerium Oxide NanoparticlesProtect Plant Photosynthesis from Abiotic Stress by Scavenging ReactiveOxygen Species.ACS Nano vol.11 11283-11297(2017).

[0510] 33.Lv,J.,Christie,P.&Zhang,S.Uptake,translocation,and transformationof metal-based nanoparticles in plants:recent advances and methodologicalchallenges.Environmental Science:Nano 6,41-59(2019).

[0511] 34.Raliya,R.,Nair,R.,Chavalmane,S.,Wang,W.-N.&Biswas,P.Mechanisticevaluation of translocation and physiological impact of titanium dioxide andzinc oxide nanoparticles on the tomato(Solanum lycopersicum L.)plant.Metallomics 7,1584-1594(2015).

[0512] 35.Hussain,H.I.,Yi,Z.,Rookes,J.E.,Kong,L.X.&Cahill,D.M.Mesoporoussilica nanoparticles as a biomolecule delivery vehicle inplants.J.Nanopart.Res.15,1676(2013).

[0513] 36.Borgatta,J.et al.Copper Based Nanomaterials Suppress Root FungalDisease in Watermelon(Citrullus lanatus):Role of Particle Morphology,Composition and Dissolution Behavior.ACS Sustainable Chem.Eng.6,14847-14856(2018).

[0514] 37. Ma, C. et al. Advanced material modulation of nutritional and phytohormone status alleviates damage from soybean sudden deathsyndrome. Nat. Nanotechnol. (2020) doi: 10.1038 / s41565-020-00776-1.

[0515] Example 2. Targeted delivery to fungi via biorecognition using glucose-coated carbon dots

[0516] Nanocarriers are designed herein that target active ingredients to fungi in plants by recognizing glucose transporters (GUTs) on fungal cell membranes. The β- or γ-cyclodextrin / glucose-coated Gd-doped carbon dots (glu-β-GdCD) nanocarriers described in this example comprise three components: a biorecognition moiety (glucose), fluorescent nanoparticles (carbon dots), and a molecular basket for loading fungicides. Glucose-coated nanocarriers have a higher binding affinity for fungal cells, which is mediated by biorecognition between glucose and GUT membrane proteins on the surface of the nanoparticles. An increase in nanoparticle thickness was also observed after functionalization with a molecular basket (Figure 14).

[0517] Enhanced delivery to fungi using glucose-functionalized nanocarriers was demonstrated in an in vitro assay, where GFP Botrytis hyphae were incubated with the nanocarriers, then washed with DI water, and then imaged with confocal microscopy. Representative confocal images of GFP Botrytis exposed to the nanocarriers showed enhanced uptake of glucose-coated glu-β-GdCD by the fungus ( FIG. 15 b ). Colocalization analysis of GdCD with GFP Botrytis fluorescence signals showed that the percentage of GFP colocalized with targeted glu-β-GdCD was significantly higher than that of control counterparts without glucose coating ( FIG. 15 c ). Orthogonal views of z-stacked confocal images of GFP Botrytis were performed using line cross-sections, and overlap of fluorescence peaks corresponding to GFP and GdCD was shown ( FIG. 15 d ).

[0518] Targeted delivery of nanocarriers coated with glucose to fungi was also tested in infected leaves. In vivo confocal images of leaves infected with GFP Botrytis cinerea showed that compared with non-targeted nanocarriers (β-GdCD), the colocalization degree of nanocarriers coated with glucose (glu-β-GdCD and glu-γ-GdCD) with GFP fluorescence was higher (Figure 16a). It was shown that compared with β-GdCD, the colocalization rate of glu-β-GdCD and GFP was enhanced (Figure 16b). Orthogonal views from Z stack confocal images showed the colocalization of glu-β-GdCD in GFP Botrytis cinerea (Figure 16c).

[0519] The in vitro delivery of fluorescent chemical cargo to fungi mediated by nanocarriers was evaluated. The fluorescence spectrum of R6G in the presence of different concentrations of β-cyclodextrin (0-10mM, TES buffer, pH 7.4) was evaluated (Figure 17b). The dose-dependent fluorescence response of R6G interacting with β-cyclodextrin and γ-cyclodextrin was evaluated (Figure 17c). The confocal images of leaves infected with GFP Botrytis cinerea showed that compared with non-targeted nanocarriers (β-GdCD and γ-GdCD), the co-localization degree of nanocarriers (glu-β-GdCD and glu-γ-GdCD) coated with glucose was higher (Figure 17d) with GFP fluorescence. It was shown that compared with γ-GdCD, the co-localization rate of glu-γ-GdCD and GFP was enhanced (Figure 17e). From the orthogonal view of the z-stacked confocal image, R6G was co-localized with glu-γ-GdCD in GFP Botrytis cinerea (Figure 17f).

[0520] Targeted delivery of fluorescent chemical cargoes mediated by nanocarriers to fungi in infected leaves was tested and demonstrated herein. Confocal images of GFP Botrytis infected leaves showed a higher degree of colocalization of R6G delivered by glu-γ-GdCD with GFP fluorescence than non-targeted γ-GdCD (FIG. 18a). The colocalization rate of R6G delivered by glu-γ-GdCD with GFP was compared with γ-GdCD (FIG. 18b). Orthogonal views of Z stacks from confocal images showing colocalization of glu-β-GdCD within GFP Botrytis (FIG. 18c).

[0521] method

[0522] Synthesis of sucrose or glucose and β-cyclodextrin coated carbon dots (suc-B-CD or glu-B-CD). suc-B-CD or gluc-B-CD was synthesized by coating the CD core with β-cyclodextrin and sucrose or glucose. The core carbon dots (CD) were synthesized by slight modifications of a previously reported protocol (Hu et al. ACS Nano 2020, 14, 7, 7970-7986). The CD core was synthesized by a hydrothermal reaction using citric acid, urea, and ammonium hydroxide. In brief, 1.92 g of citric acid (Fisher, 99.7%) and 2.40 g of urea (Fisher, 99.2%) were dissolved in 2 mL of DI water, and 1.35 mL of ammonium hydroxide (SigmaAldrich, NH 3 ·H 2 The mixture was reacted at 180 ° C for 1.5 h, cooled to room temperature, and redissolved in DI water. Aggregates were removed by centrifugation at 4,500 rpm for 30 min. The solution was further filtered using a syringe filter (Whatman, pore size 0.02 μm) to remove larger particles. Next, the CD core was functionalized to BA-terminated CD (BA-CD) by carboxyphenylboronic acid (CBA). NHS (75 nmol) and EDC / HCl (75 nmol) were added to the CD in TES buffer (10 mM TES buffer, pH 7.4). Then, the mixture was vortexed (750 rpm) for 15 min at ambient temperature. CBA solution (75 nmol) was added and reacted at room temperature for 3 h. In order to wash off excess CBA, a dialysis membrane (1K MWCO, Spectrum Laboratories) was used and dialyzed with 2 L DI water. In order to introduce β-cyclodextrin and sucrose or glucose to sucCD or gluCD, BA-CD was first dispersed in TES buffer (10 mM TES buffer; pH 10.4), then 10 ul of 5 mM β-cyclodextrin was added and stirred overnight. After reaction with β-cyclodextrin, the mixture was washed with a dialysis membrane (1K MWCO, Spectrum Laboratories) by dialyzing with 2 L DI water. Subsequently, sucrose or glucose was reacted with β-cyclodextrin by repeating the same protocol to make suc-B-CD or gluc-B-CD, respectively.

[0523] For the fungal assay of the targeted delivery of nanocarriers, a small amount of GFP Botrytis is collected from the agar plate in 1ml growth medium using a sterile exchanger (sterile swap), to isolate the spores of GFP Botrytis, and filter to separate spores from hyphae. Spores are counted using a hemocytometer, and diluted to 5 spores / ul, and 3ul suspension is transferred to the hole of a microscope slide (μ-Slide 18 holes, ibidi). 3ul suspension is transferred to the hole of a microscope slide (μ-Slide 18 holes, ibidi) and hatched for 72h. After hatching, Botrytis hyphae and nanocarrier (5uL nanocarrier (0.1mg / ml, with 0.1 wt% Silwet L-77)) are hatched for 1h, and analyzed using confocal fluorescence microscopy.

[0524] Example 3. Targeted delivery to fungi via biorecognition

[0525] After growing Botrytis cinerea hyphae on a microscope slide, the samples were incubated with uncoated nanocarriers and sucrose or glucose-coated nanocarriers for one hour and then observed under a confocal microscope. Both uncoated GdCD and GdCD coated with sucrose or glucose showed fluorescent signals in Botrytis cinerea ( Fig. 20 ). GdCD coated with glucose showed the strongest fluorescence signal in the confocal image. Fig. 20 ) showed that nanocarriers coated with glucose could enter Botrytis cinerea more effectively.

[0526] Genetically engineered Botrytis mycelium expressing GFP protein was cultured on microscope slides and the experiment was performed using Fig. 20 The same method is used. Fig.21 ), the degree of colocalization between the fluorescent signals of GdCD and GFP was calculated, showing similar levels of 85-92% for uncoated GdCD and GdCD coated with sucrose or glucose. GdCD coated with sucrose (85%) showed a slightly lower level compared to uncoated GdCD (90%), which was attributed to a certain amount of GdCD not only attached to the inside but also to the outside of the fungal wall. GdCD coated with glucose (92%) showed slightly increased colocalization and a clear yellow color due to colocalization with GFP within Botrytis fungi. However, this preliminary experiment was based on one replicate, and in order to ensure the reproducibility of the experiment ( Fig.21 ), more biological replicates are needed. Overall, this in vitro experiment showed that the nanocarriers can enter the GFP Botrytis fungus.

[0527] method

[0528] Synthesis of β-cyclodextrin coated Gd-doped carbon dots (β-GdCD). 0.2g gadolinium chloride hexahydrate, 0.5g citric acid and 0.17ml diethylenetriamine were dissolved in 6mL DI water. The mixture was transferred to a high pressure reactor and reacted for 1.5h at 180°C. After the reaction, the mixture was cooled to room temperature and aggregates were removed by centrifugation at 4,500rpm for 30min. The supernatant was then transferred to a dialysis membrane (1kDa MWCO) and dialyzed with 2L water to remove excess reagents from the solution. The solution was further filtered using a syringe filter (Whatman, pore size 0.02μm) to remove larger particles. Next, the GdCD core was functionalized to BA-terminated GdCD (BA-GdCD) by carboxyphenylboronic acid (CBA). NHS (75 nmol) and EDC / HCl (75 nmol) were added to GdCD in TES buffer (10 mM TES buffer, pH 7.4). The mixture was then stirred (500 rpm) for 30 min at ambient temperature. CBA solution (75 nmol) was added and reacted at room temperature for 3 h. In order to wash off the excess CBA, a dialysis membrane (1K MWCO, Spectrum Laboratories) was used and dialyzed with 2 LDI water. In order to introduce β-cyclodextrin onto BA-GdCD, BA-GdCD was first dispersed in TES buffer (10 mM TES buffer; pH 10.4), then 10 ul of 5 mM β-cyclodextrin was added and stirred for 3 h. After reacting with β-cyclodextrin, the mixture was washed with a dialysis membrane (1K MWCO, Spectrum Laboratories) by dialyzing with 2 LDI water.

[0529] Synthesis of sucrose or glucose coated nanocarriers (suc-β-GdCD, glu-β-GdCD). For sucrose or glucose coated nanocarriers, β-GdCD was dispersed in TES buffer (10 mM TES buffer; pH 10.4), then 10 ul of 6 mM sucrose or glucose solution was added and stirred for 3 h. The mixture was washed with a dialysis membrane (1KMWCO, Spectrum Laboratories) by dialysis with 2 L DI water.

[0530] Prepare the Botrytis mycelia of nanocarrier treatment on microscope slide for confocal microscopy analysis.For the in vitro fungal assay of the absorption of nanocarrier, a small amount of GFP Botrytis is collected from the agar plate in 1ml growth medium by using a sterile exchanger to isolate the spores of GFP Botrytis, and filter to separate spores from mycelia. Use a hemocytometer to count spores, and dilute to 5 spores / ul. 3ul suspension is transferred to the hole of microscope slide (μ-Slide 18 holes, ibidi). 3ul suspension is transferred to the hole of microscope slide (μ-Slide 18 holes, ibidi) and hatched 72h. After hatching, Botrytis mycelia and nanocarrier (5uL nanocarrier (0.1mg / ml, with 0.1 wt% Silwet L-77)) are hatched for 1h, and analyzed using confocal fluorescence microscope.

[0531] Confocal fluorescence microscopy imaging. Nanocarrier-treated Botrytis cinerea was imaged using a Zeiss laser scanning confocal microscope, Zeiss 880. Imaging settings were as follows: ×40 wet objective; 355 nm laser excitation for GdCD; 488 nm for GFP. PMT detection ranges were set to: 400-480 nm for GdCD; 500-550 nm for GFP.

[0532] Example 4. Testing the delivery of functionalized sucrose-coated nanoparticles to grapevine fungal structures

[0533] like Figure 24-25 As shown, enhanced in vivo delivery of sucrose-coated nanocarriers to Botrytis sp. fungi in grapevine plants was detected compared to uncoated nanocarriers.

[0534] Nanocarrier-treated Botrytis hyphae were prepared on grapevine leaves for confocal microscopy analysis. Detached leaf assays were performed to perform in vivo fungal assays for nanocarrier uptake in grapevine leaves. To collect spores for leaf inoculation, a small amount of GFP Botrytis was collected from an agar plate in 1 ml growth medium using a sterile exchanger to isolate GFP Botrytis spores and filtered using autoclaved cheesecloth to separate the spores from the hyphae. Spores were counted using a hemocytometer and diluted to 10 spores / ul. Using 10ul spore suspension, a pipette was used to inoculate the adaxial surface (top) of the leaf. Detached GFP Botrytis infected leaves were placed in PDA agar plates, sealed, and allowed to grow for 72h. After incubation, Botrytis hyphae were incubated with nanocarriers (1.5uL nanocarrier (0.1mg / ml, with 0.1 wt% Silwet L-77)) for 3h and analyzed using confocal fluorescence microscopy.

[0535] Confocal fluorescence microscopy imagingNanocarrier treated GFP Botrytis cinerea was imaged by Zeiss laser scanning confocal microscope Zeiss 880. Imaging settings were as follows: ×40 wet objective; 355 nm laser excitation for GdCD; 488 nm for GFP. PMT detection ranges were set to: 400-480 nm for GdCD; 500-550 nm for GFP.

[0536] Synthesis of Gd-doped Carbon Dots (GdCD) . 0.2g of gadolinium chloride hexahydrate, 0.5g of citric acid and 0.17ml of diethylenetriamine were dissolved in 6mL of DI water. The mixture was transferred to a high pressure reactor and reacted at 180°C for 1.5h. After the reaction, the mixture was cooled to room temperature and aggregates were removed by centrifugation at 4,500rpm for 30min. The supernatant was then transferred to a dialysis membrane (1kDa MWCO) and dialyzed with 2L of water to remove excess reagent from the solution. The solution was further filtered using a syringe filter (Whatman, pore size 0.02μm) to remove larger particles.

[0537] Synthesis of sucrose-coated nanocarrier (suc-β-GdCD) For sucrose-coated nanocarriers, β-GdCD was dispersed in TES buffer (10 mM TES buffer; pH 10.4), then 10 ul of 6 mM sucrose solution was added and stirred for 3 h. The mixture was washed with a dialysis membrane (1K MWCO, Spectrum Laboratories) by dialyzing against 2 L DI water.

[0538] All publications, patents and patent documents are incorporated herein by reference as if individually incorporated by reference. The present invention has been described with reference to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the present invention.

Claims

1. A conjugate comprising a glucose transporter (GUT) targeting agent linked to a cargo that is a pesticide, herbicide or fertilizer.

2. The conjugate of claim 1, wherein the cargo is a pesticide, and wherein the pesticide is a fungicide.

3. The conjugate of claim 1 or 2, further comprising nanoparticles and / or molecular baskets, wherein the nanoparticles are selected from the group consisting of quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, and metal or metal oxide nanoparticles.

4. The conjugate of claim 3, comprising nanoparticles linked to one or more GUT targeting agents.

5. The conjugate of claim 3 or 4, wherein the cargo is associated with the nanoparticle or with the molecular basket.

6. The conjugate of claim 5, wherein the cargo is associated with the nanoparticle.

7. The conjugate of claim 5, wherein the cargo is associated with the molecular basket.

8. The conjugate of any one of claims 3 to 7, wherein the molecular basket comprises beta cyclodextrin or gamma cyclodextrin.

9. The conjugate of claim 8, wherein the cargo forms an inclusion complex with the cyclodextrin.

10. The conjugate of claim 9, wherein the cargo is selected from the group consisting of: oxazolidinone, benzathiapiprolin, thiophanate-methyl, cyazolin, diastereamide, ethiconazole, fluopyram, myclobutanil, fluthiazolin, pyraclostrobin, thiabendazim and spiroxabiocin.

11. The conjugate of any one of claims 3 to 6, comprising a conjugate of formula I: NP—(Connector—TA) n (I) in: NP is the nanoparticle; TA is the glucose transporter (GUT) targeting agent; the linker has a molecular weight of about 20 Daltons to about 20,000 Daltons; and n is an integer ≥1.

12. The conjugate of claim 11, wherein the NP is further functionalized with one or more molecular baskets.

13. The conjugate of claim 12, wherein the molecular basket comprises beta cyclodextrin or gamma cyclodextrin.

14. The conjugate of claim 12 or 13, wherein the cargo is associated with the molecular basket.

15. The conjugate of claim 13, wherein the cargo forms an inclusion complex with the cyclodextrin.

16. The conjugate of any one of claims 12 to 15, wherein the cargo is selected from the group consisting of: oxazolidinone, benzathiapiprolin, ethiconazole, fluopyram, fluthiazolin and spiroxabiocin.

17. The conjugate according to claim 1, which is a conjugate of formula II: Cargo-Connector-TA(II) in: TA is the glucose transporter (GUT) targeting agent; and the linker has a molecular weight of about 20 Daltons to about 20,000 Daltons.

18. The conjugate of any one of claims 7 to 10, comprising a conjugate of formula III: MB—(Connector—TA) n (III) in: MB is the molecular basket; TA is the glucose transporter targeting agent (GUT) targeting agent; the linker has a molecular weight of about 20 Daltons to about 20,000 Daltons; and n is an integer ≥1.

19. The conjugate of any one of claims 11 to 18, wherein the linker has a molecular weight of about 20 Daltons to about 5,000 Daltons.

20. The conjugate of any one of claims 11 to 18, wherein the linker has a molecular weight of about 20 Daltons to about 1,000 Daltons.

21. The conjugate of any one of claims 11 to 20, wherein the linker comprises a boronic acid group -B(O-)2, wherein each O- is bonded to TA.

22. The conjugate of any one of claims 11 to 21, wherein the linker has the structure -XYZ-; wherein: X is a bond, -O-, -S-, -C(=O)-, -N(R a )-, -C(=O)NH-, -C(=S)NH-, -C(=O)O-, -C(=O)S-, -NHSO2-, -OC(=O)NH-, -NHC(=O)NH-, -NHC(=S)NH-, -Si(R b )3 or -B(R c )2, Z is a bond, -O-, -S-, -C(=O)-, -N(R a )-, -C(=O)NH-, -C(=S)NH-, -C(=O)O-, -C(=O)S-, -NHSO2-, -OC(=O)NH-, -NHC(=O)NH-, -NHC(=S)NH-, -Si(R b )3 or -B(R c )2; R a is H or (C1-C6) alkyl; Each R b are independently O-, -OH or (C 1- C4) alkoxy; Each R c is O- connected to TA; Y is a divalent, saturated or unsaturated, branched or unbranched chain (C2-C 18 ) hydrocarbon chain, wherein one or more carbons of the hydrocarbon chain are optionally replaced by -O-, -N(R s )-, -S-, aryl or heteroaryl, and wherein the hydrocarbon chain is optionally substituted on carbon with one or more substituents selected from the group consisting of halo, hydroxy, thiol, oxo (=O) and thioxo (=S); and R s is H or (C1-C6) alkyl.

23. The conjugate of claim 22, wherein Z is -B(R c )2.

24. The conjugate of any one of claims 1 to 23, wherein the glucose transporter (GUT) targeting agent is a monosaccharide.

25. The conjugate of any one of claims 1 to 23, wherein the glucose transporter (GUT) targeting agent is glucose.

26. The conjugate of claim 11, comprising Formula Ib3, Formula Ib4, Formula Ic3 or Formula Ic4:

27. The conjugate of claim 12, comprising a conjugate of formula Ie: (MB—Connector) m —NP—(Connector—TA) n (Formula Ie) in: MB is the molecular basket; NP is the nanoparticle; TA is the glucose transporter (GUT) targeting agent; each linker is independently selected from linkers having a molecular weight of about 20 Daltons to about 20,000 Daltons; m is an integer ≥1; and n is an integer ≥1.

28. The conjugate of claim 27, comprising Formula Ie3 or Formula Ie4:

29. The conjugate of any one of claims 3 to 16 and 19 to 28, wherein the nanoparticles are selected from the group consisting of carbon dots, carbon nanotubes, silica nanoparticles, metal or metal oxide nanoparticles, lipid nanoparticles and liposomes.

30. The conjugate of any one of claims 3 to 16 and 19 to 28, wherein the nanoparticle has a diameter of about 1 nm to 300 nm.

31. The conjugate of any one of claims 3 to 16 and 19 to 28, wherein the nanoparticles have a diameter of about 5 nm to 150 nm.

32. The conjugate of any one of claims 3 to 16 and 19 to 28, wherein the nanoparticles have a diameter of about 1 nm to 50 nm.

33. The conjugate of any one of claims 1 to 32, wherein the cargo has a molecular weight of less than 1000 g / mol.

34. A method of treating a fungal infection in a plant or introducing a conjugate into a fungus, the method comprising: The plant and / or fungus is contacted with the conjugate of any one of claims 1 to 33.

35. The method of claim 34, comprising contacting the fungus with the conjugate.

36. The method of claim 34, wherein the plant is suffering from a fungal infection selected from the group consisting of gray mold, anthracnose, leaf blight, leaf spot, leaf rust, gall rust, wilt, early blight, and powdery mildew.

37. The method of claim 34, wherein the leaves, stems and / or roots of the plant are infected by the fungus.

38. The method of claim 34, wherein leaves and / or fruits of the plant are infected by the fungus.

39. The method of any one of claims 34 to 38, wherein the plant is infected with a fungus selected from the group consisting of Alternaria spp., Diplodia spp., Botrytis spp., Coccidiales spp., Colletotrichum spp., Powdery Mildew spp., Puccinia spp., Fusarium spp., Aspergillus spp., Puccinia spp., and Puccinia spp.

40. The method of any one of claims 34 to 38, wherein the fungus is selected from the group consisting of Psoralea oryzae, certain species of Botrytis (e.g., Botrytis cinerea), certain species of Puccinia spp., Fusarium graminearum, Fusarium oxysporum, Blepharitis brucei, Mycosphaeria graminearum, certain species of Colletotrichum spp., Ustilago maydis, Puccinia flax, and Psora tritici.

41. The method of any one of claims 34 to 40, wherein the conjugate is contacted with the plant and / or fungus during germination.

42. The method of any one of claims 34 to 40, wherein the conjugate is contacted with the plant and / or fungus after germination.

43. The method of any one of claims 34 to 40, wherein the conjugate is contacted with the plant and / or fungus during proliferation.

44. The method of any one of claims 34 to 40, wherein the conjugate is contacted with the fungus while the fungus is forming hyphae.

45. The method of any one of claims 34 to 40, wherein the conjugate is contacted with the plant and / or fungus during sporulation.

46. ​​A method for introducing a conjugate into a fungus, comprising contacting the fungus with a conjugate comprising nanoparticles and / or molecular baskets linked to a glucose transporter (GUT) targeting agent, wherein the nanoparticles are selected from the group consisting of quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, and metal or metal oxide nanoparticles.

47. The method of claim 46, wherein the conjugate is contacted with the fungus during germination.

48. The method of claim 46, wherein the conjugate is contacted with the fungus after germination.

49. The method of claim 46, wherein the conjugate is contacted with the fungus during proliferation.

50. The method of claim 46, wherein the conjugate is contacted with the fungus while the fungus is forming hyphae.

51. The method of claim 46, wherein the conjugate is contacted with the fungus during sporulation.

52. A conjugate comprising a glucose transporter (GUT) targeting agent attached to a nanoparticle, wherein the conjugate is capable of being delivered to a fungus and the nanoparticle is selected from the group consisting of quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, and metal or metal oxide nanoparticles.

53. The conjugate of claim 52, comprising a conjugate of formula I: NP—(Connector—TA) n (I) in: NP is a nanoparticle selected from the group consisting of: quantum dots, carbon dots, carbon nanotubes, silica nanoparticles (e.g., porous silica nanoparticles), lipid nanoparticles, liposomes, and metal or metal oxide nanoparticles; TA is the glucose transporter (GUT) targeting agent; the linker has a molecular weight of about 20 Daltons to about 20,000 Daltons; and n is an integer ≥1.

54. The conjugate of claim 53, wherein the nanoparticles are selected from carbon dots, carbon nanotubes, silica nanoparticles (eg, porous silica nanoparticles), lipid nanoparticles, and liposomes.

55. The conjugate of any one of claims 52 to 54, which does not comprise a cargo.

56. The conjugate of any one of claims 52 to 54, comprising a cargo.

57. The conjugate of any one of claims 52 to 56, wherein TA is a monosaccharide.

58. The conjugate of any one of claims 52 to 56, wherein TA is a hexose.

59. The conjugate of any one of claims 52 to 56, wherein TA is glucose.

60. A method comprising detecting the conjugate of any one of claims 52 to 59 in a fungus.

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