A rare earth-framework nucleic acid nanocomposite material and its preparation method and application

Abstract

The present invention discloses a rare earth-framework nucleic acid nanocomposite material and its preparation method and application, belonging to the technical field of rare earth biomaterials. The rare earth-framework nucleic acid nanocomposite material comprises a framework nucleic acid and a rare earth mineralization layer deposited on the surface of the framework nucleic acid. The rare earth-framework nucleic acid nanocomposite material of the present invention has good biocompatibility as well as luminescent and catalytic properties. The preparation method uses the framework nucleic acid structure with freely designable nano-sized shape as a growth template for the rare earth mineralization layer, guides the rare earth ions to adsorb, deposit and grow thereon to form a rare earth mineralization layer, realizes the structural designability of rare earth biomaterials, and is of great significance to the application and development of rare earth biomaterials in bioimaging, biotherapy and other high-tech fields.

Description

Technical Field

[0001] The present invention relates to the technical field of rare earth biomaterials, and in particular to a rare earth-framework nucleic acid nanocomposite material and a preparation method and application thereof. Background Art

[0002] With the development of nanomaterials, rare earth nanomaterials have been widely used in cell imaging, immunoassays, and DNA detection. Among them, rare earth nanoluminescent materials have the characteristics of deep penetration, low background interference, and good stability, and are often used in in vivo biological imaging. In addition, rare earth elements also have valence-changing catalytic properties, which can inhibit tumor cells, remove free radicals in the body, change the microtubule structure of cancer cells, and reduce the growth ability of tumors. Therefore, rare earth nanomaterials have important research significance and medical value. However, how to achieve the controllable assembly and precise structural regulation of rare earth upconversion nanoparticles and biorecognition molecules is still a difficult problem in current research.

[0003] Traditional rare earth nanoluminescent materials are usually spherical or symmetrical solid forms. The singleness of structure and function limits the application and development of rare earth bio-nanomaterials in bio-imaging therapy and other high-tech fields. The functional diversity guided by the multiple coordination of rare earth with DNA and the diversity of framework nucleic acid structure helps to promote the development of new biotechnology materials. Therefore, it is very important to study and develop rare earth bioluminescent materials based on framework nucleic acids. Summary of the invention

[0004] In view of this, the technical problem to be solved by the present invention is to provide a rare earth-framework nucleic acid nanocomposite material and a preparation method and application thereof. The rare earth-framework nucleic acid nanocomposite material has controllable shape and uniform distribution.

[0005] In order to achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0006] The invention provides a rare earth-framework nucleic acid nanocomposite material, comprising a framework nucleic acid and a rare earth mineralization layer deposited on the surface of the framework nucleic acid.

[0007] The rare earth-framework nucleic acid nanocomposite material of the present invention uses the framework nucleic acid as a template to guide the rare earth ions to be adsorbed, deposited and grown thereon to form a rare earth mineralization layer.

[0008] The above framework nucleic acid template has structural designability, and the framework nucleic acid can be self-assembled into a designed shape by changing the DNA or RNA sequence to form a preset structure.

[0009] The invention uses framework nucleic acid as a template, so that the biocompatibility of the rare earth-framework nucleic acid nanocomposite material is greatly improved.

[0010] In some specific embodiments of the present invention, the shape of the framework nucleic acid includes but is not limited to one or more of a rod, a triangle, a square, and a tetrahedron; more preferably one or more of a rod, a triangle, and a tetrahedron.

[0011] Preferably, the rare earth mineralized layer is selected from one or more of inorganic salts, oxides and hydroxides of rare earth ions.

[0012] The inorganic salts of the above rare earth ions include, but are not limited to, chlorides, nitrates, sulfates, acetates, oxalates, phosphates and the like.

[0013] In the present invention, the rare earth mineralization layer is mixed and doped with different rare earth ions in different proportions, thereby providing specific luminescence and catalytic properties.

[0014] Preferably, the rare earth ions are selected from one or more of La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Y, and Sc; more preferably, the rare earth ions are selected from one or more of Ce, Yb, Er, Tm, Ho, Y, Sm, Dy, Tb, and Eu.

[0015] The rare earth-framework nucleic acid nanocomposite material of the present invention has controllable shape and uniform distribution, and has good biocompatibility and specific luminescence and catalytic properties.

[0016] The present invention also provides a method for preparing a rare earth-framework nucleic acid nanocomposite material, comprising the following steps: after the framework nucleic acid and the mineralized growth liquid are evenly mixed, the mineralized growth liquid is deposited and grown on the surface of the framework nucleic acid to form a rare earth mineralized layer, thereby preparing the rare earth-framework nucleic acid nanocomposite material.

[0017] The mineralization growth solution in the present invention is a mixed solution of rare earth ions and counter ions.

[0018] The rare earth ions of the present invention are connected to the framework nucleic acid structure template through electrostatic action and coordination action, and are deposited and grown on the surface thereof to form a rare earth mineralization layer.

[0019] Preferably, the rare earth ions are selected from one or more of La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Y, and Sc; more preferably, one or more of Ce, Yb, Er, Tm, Ho, Y, Sm, Dy, Tb, and Eu.

[0020] In the present invention, the framework nucleic acid structure is used as a nano-sized shape template to guide the rare earth ions to deposit and grow thereon. The electrostatic interaction and coordination between the bases and phosphate groups of the nucleic acid molecules in the framework nucleic acid and the rare earth ions adsorb the rare earth ions on the framework nucleic acid structure template. Then, the rare earth ion inorganic salt (or oxide or hydroxide) continues to deposit and grow on the template to form a nanostructure.

[0021] Since the interaction between rare earth and framework nucleic acid is strong, too many rare earth ions will cause the destruction of the framework nucleic acid template structure. Therefore, the balance ions in the mineralization growth solution effectively weaken the interaction between rare earth ions and nucleic acids through competition, which not only ensures the slow adsorption and deposition growth of rare earth ions on the template, but also maintains the stability of the framework nucleic acid structure, and finally obtains a rare earth-framework nucleic acid nanocomposite material with a target structure.

[0022] Preferably, the counter ion is selected from one or more of alkali metal ions, alkaline earth metal ions and transition metal ions.

[0023] The alkali metal ion is more preferably a sodium ion or a potassium ion.

[0024] The alkaline earth metal ion is more preferably a magnesium ion or a calcium ion.

[0025] The transition metal ion is more preferably a copper ion or a zinc ion.

[0026] In some specific embodiments of the present invention, the counter ion is selected from magnesium ion or calcium ion.

[0027] Preferably, the concentration of the framework nucleic acid is 1 to 100 nmol / L; more preferably, 2 to 50 nmol / L; further preferably, 4 to 25 nmol / L.

[0028] In the present invention, the ratio of rare earth ions to counter ions in the mineralized growth solution needs to be controlled within a certain range to ensure that the rare earth ions are slowly adsorbed and deposited on the framework nucleic acid template and that the morphology of the framework nucleic acid template can be stably present.

[0029] Preferably, the concentration of the rare earth ions is 0.1 to 50 mmol / L; more preferably 0.5 to 10 mmol / L.

[0030] Preferably, the concentration of the counter ion is 1 to 100 mmol / L; more preferably, 2 to 50 mmol / L; further preferably, 4 to 25 mmol / L.

[0031] Preferably, the molar ratio of the rare earth ion to the counter ion is (0.001-50):1; more preferably (0.005-10):1.

[0032] In the present invention, three shapes of framework nucleic acid templates, six rare earth element combinations, and two balancing salts are used. Specifically, three shapes of framework nucleic acid templates, rod-shaped, triangle-shaped, and tetrahedral, six rare earth element combinations of Y / Yb / Er, Y / Yb / Tm, Y / Yb / Ho, Ce / Yb / Er, Ce / Yb / Tm, and Ce / Yb / Ho, and two balancing salts of magnesium chloride and magnesium acetate are used.

[0033] In the preparation method of the rare earth-framework nucleic acid nanocomposite material, the amount and proportion of reagents, reaction temperature, reaction time, pH and other conditions will affect the morphology of the nanocomposite material.

[0034] Preferably, the reaction temperature is 4°C to 40°C.

[0035] Preferably, the reaction time is 10 min to 30 d.

[0036] Preferably, the pH is 4-10.

[0037] If the amount of rare earth, the raw material for preparing rare earth framework nanostructures, is insufficient, there will be too little adsorption and growth on the framework nucleic acid template, resulting in poor luminescence and catalytic effects; if the amount is too large, the framework nucleic acid structure will be destroyed, resulting in the loss of the template shape, and the mineralized layer will grow randomly to form a disordered structure, ultimately resulting in the inability to form a rare earth framework nanomaterial with a preset shape.

[0038] The doping ratio of various rare earth elements will also affect the luminescence and catalytic effects. Different rare earth elements have different energy level transition characteristics, and thus can emit light of different wavelengths. The combination of different rare earth elements introduces more energy transfer modes, thereby producing better luminescence characteristics. Therefore, the luminescence and catalytic properties of the final prepared rare earth framework nanostructure mainly depend on the doping ratio of the various rare earth elements used.

[0039] In some specific embodiments of the present invention, six rare earth element combinations of Y / Yb / Er, Y / Yb / Tm, Y / Yb / Ho, Ce / Yb / Er, Ce / Yb / Tm, and Ce / Yb / Ho are selected as raw materials for preparing rare earth framework nanostructures, so that the rare earth-framework nucleic acid nanocomposite material has good luminescence and catalytic properties.

[0040] The preparation method prepares the rare earth-framework nucleic acid nanocomposite material by depositing rare earth ions and growing them on a framework nucleic acid template with a designable structure.

[0041] Preferably, the deposition growth method is selected from an interfacial reaction method or a solution reaction method.

[0042] The method for preparing the rare earth-framework nucleic acid nanocomposite material of the present invention specifically comprises the following steps:

[0043] A) Preparation of framework nucleic acid nanostructures of different shapes, such as rod-shaped, triangle-shaped, square-shaped, tetrahedral-shaped framework nucleic acids.

[0044] B) Interface reaction method: The framework nucleic acid nanostructure obtained in step A) is adsorbed on the interface, and then rare earth mineralization growth is performed.

[0045] The interface used can be a planar medium such as a silicon wafer, a glass sheet, or a mica sheet. By adjusting the type and concentration of adsorption-assisting ions, such as magnesium ions, calcium ions, and nickel ions, the framework nucleic acid nanostructure is assisted to be fixed to the medium plane. The plane with the framework nucleic acid fixed thereon is then immersed in a mineralization growth solution. By regulating the concentration of rare earth and counter ions in the mineralization growth solution, the pH of the solution, the reaction time, and the temperature, the rare earth elements are deposited and grown on the framework nucleic acid template to form the target rare earth-framework nucleic acid nanocomposite material.

[0046] By using the above-mentioned interfacial adsorption reaction, the framework nucleic acid template can be arranged at a certain interval on the interface, thereby effectively avoiding the aggregation of the product and greatly reducing the reaction system, which is conducive to the exploration of the initial reaction conditions. However, the amount of the product is low, it is difficult to prepare in large quantities, and the product is fixed on the interface, making it difficult to separate the product from the interface, thus limiting the application of the product to a certain extent.

[0047] C) Solution reaction method: directly disperse the framework nucleic acid nanostructure template obtained in step A) in the solution, and perform rare earth mineralization growth in the solution state. By regulating the concentration of framework nucleic acid, rare earth ions, and counter ions in the solution and the pH of the solution, the reaction time, and the temperature, the rare earth ions are deposited and grown using the framework nucleic acid nanostructure as a template, and finally a rare earth-framework nucleic acid composite material that inherits the template nanostructure is formed.

[0048] By adopting the above-mentioned solution adsorption reaction, the preparation of rare earth-framework nucleic acid nanocomposites in the solution can obtain the target product in large quantities and is easy to expand the application. However, the rare earth mineralization layer is prone to random nucleation and growth in the solution, and the growth rate of the rare earth mineralization layer is difficult to control, resulting in excessive growth, and ultimately leading to product aggregation, resulting in failure in the preparation of rare earth-framework nucleic acid nanocomposites. However, the introduction of counterions can effectively improve this problem, slow down the deposition growth rate of the rare earth mineralization layer, and ensure that the rare earth mineralization layer grows according to the framework nucleic acid template.

[0049] The present invention also provides the use of the rare earth-framework nucleic acid nanocomposite material or the rare earth-framework nucleic acid nanocomposite material prepared by the above preparation method in high-resolution single particle fluorescence imaging or nanocatalysis.

[0050] Compared with the prior art, the rare earth-framework nucleic acid nanocomposite provided by the present invention comprises a framework nucleic acid and a rare earth mineralization layer deposited on the surface of the framework nucleic acid. The rare earth-framework nucleic acid nanocomposite described in the present invention has good biocompatibility and luminescence and catalytic properties. The preparation method uses the framework nucleic acid structure with freely designable nano-sized shape as a growth template for the rare earth mineralization layer, guides the rare earth ions to adsorb, deposit and grow thereon to form the rare earth mineralization layer, realizes the structural designability of rare earth nanomaterials, and is of great significance to the application and development of rare earth nanomaterials in biological imaging and treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 The schematic diagram of the synthesis of the rare earth-framework nucleic acid nanocomposite material in Example 1 and the transmission electron microscope image and high-resolution fluorescence microscope characterization image;

[0052] Figure 2 Atomic force microscopy images of rare earth-nucleic acid nanocomposites with different morphologies (rod-shaped, triangle-shaped, and tetrahedron-shaped) in Example 1;

[0053] Figure 3 This is a transmission electron microscopy image of the rare earth-framework nucleic acid nanocomposite material in Example 2;

[0054] Figure 4 The fluorescence spectrum and polarized fluorescence diagram of the rare earth-nucleic acid nanocomposite material in Example 2 are shown. DETAILED DESCRIPTION

[0055] In order to further illustrate the present invention, the rare earth-framework nucleic acid nanocomposite material provided by the present invention and its preparation method and application are described in detail below in conjunction with examples.

[0056] The invention combines the framework nucleic acid nanostructure and the rare earth element to obtain the rare earth-framework nucleic acid nanocomposite material having both good biocompatibility and special luminescent catalytic performance.

[0057] In the present invention, the framework nucleic acid nanostructure can be formed by self-assembly of nucleic acid molecules (DNA or RNA) through complementary base pairing.

[0058] For example, the assembly primitives of commonly used framework nucleic acid nanostructures are a long circular single-stranded DNA and about 100-300 linear short single-stranded DNAs. The long circular single-stranded DNA is the backbone chain, and the linear short single-stranded DNA is the staple chain. The staple chain is paired with the corresponding complementary sequence segments on the backbone chain, and the backbone chain is bent, folded and fixed according to the design. Multiple staple chains work together to fix the backbone chain into a preset shape, and finally form the target framework nucleic acid nanostructure.

[0059] By changing the sequence of the staple chain, the final assembled nano shape can be freely designed. The framework nucleic acid has a precise nanoscale structure. Since the sequence of the assembly element nucleic acid and its position in the final framework nucleic acid nanostructure are completely known, the framework nucleic acid has excellent nanoscale precise addressing properties. In addition, since its components are entirely biological macromolecular nucleic acids, the framework nucleic acid nanostructure has good biocompatibility.

[0060] Rare earth elements have unique 4f5d electronic structures and rich energy levels, thus showing special electromagnetic properties, especially excellent luminescence performance. When doped with specific rare earth element types and proportions, rare earth nanomaterials can show excellent up-conversion luminescence properties through excited state absorption, energy transfer and cooperative sensitization.

[0061] The reaction raw materials and solvents used below are all common commercially available products.

[0062] Example 1

[0063] (1) Synthesis of framework nucleic acid nanostructures

[0064] The staple single-stranded DNA of a specific sequence and the backbone single-stranded DNA were dissolved in TAE buffer at pH = 7.4 and mixed thoroughly at a molar concentration of 10:1. Through programmed temperature control, the DNA double strands were denatured and unwound at a high temperature of 95°C, and the single-stranded complementary strands were hybridized to form double strands at a low temperature of 25°C, and rod-shaped (one-dimensional), triangle (two-dimensional) and tetrahedral (three-dimensional) nanoframe nucleic acids were obtained. Finally, the excess staple chains were removed by ultrafiltration with a molecular weight cutoff of 100kDa. The final framework nucleic acid concentration was calculated using absorbance testing. Since too high a backbone concentration would lead to aggregation, the backbone concentration was adjusted to achieve a framework nucleic acid concentration of 1 to 100nmol / L.

[0065] (2) Solution preparation of rare earth-framework nucleic acid nanostructures

[0066] Step 1: Prepare mineralization growth solution. The mineralization growth solution is a mixed solution of rare earth ions and counter ions, wherein the rare earth ions are rare earth nitrates with Ce:Yb:Er=89:10:1 (molar ratio) and the concentration is 1mmol / L; the counter ions are magnesium ions with a concentration of 10mmol / L.

[0067] Step 2: Prepare rare earth-framework nucleic acid nanostructures in solution. Add three shapes of framework nucleic acids to the mineralized growth solution and incubate at 37°C for 1 to 7 days. Ultrafiltration is used to concentrate the rare earth-framework nucleic acid nanostructures and remove various ions in the dispersion, followed by characterization by atomic force microscopy, transmission electron microscopy and other means.

[0068] Figure 1 The schematic diagram of the synthesis of the rare earth-framework nucleic acid nanocomposite material in Example 1 and the transmission electron microscope image and high-resolution fluorescence microscope characterization image;

[0069] The framework nucleic acid has three morphologies, namely rod-shaped (one-dimensional), triangle (two-dimensional) and tetrahedron (three-dimensional). The invention uses the framework nucleic acid of freely designable nano-sized shape as the growth template of the rare earth material, thereby improving the biocompatibility of the rare earth nanomaterial.

[0070] Figure 2 The atomic force microscope images of the rare earth-framework nucleic acid nanocomposites of different morphologies (rod, triangle and tetrahedron) in Example 1 show that the rare earth-nucleic acid nanocomposites are controllable in shape and uniformly distributed.

[0071] Example 2

[0072] (1) Synthesis of framework nucleic acid nanostructures

[0073] The staple single-stranded DNA of a specific sequence and the backbone single-stranded DNA were dissolved in TAE buffer at pH = 7.4 and fully mixed at a molar concentration of 10:1. Through programmed temperature control, the DNA double strands were denatured and unwound at a high temperature of 95°C, and the single-stranded complementary strands were hybridized to form double strands at a low temperature of 25°C, and a tetrahedral nanoframe nucleic acid was obtained. Finally, the excess staple chains were removed by ultrafiltration with a molecular weight cutoff of 100kDa. The final framework nucleic acid concentration was calculated using absorbance testing. Since too high a backbone concentration would lead to aggregation, the backbone concentration was adjusted to achieve a framework nucleic acid concentration of 1 to 100nmol / L.

[0074] (2) Interface-assisted preparation of rare earth-framework nucleic acid nanostructures

[0075] Step 1: Clean the flat medium. For mica sheets, just use tape to peel off the surface mica to expose the clean mica plane underneath. For silicon wafers, glass sheets and other media, soak them in Piranha Solution (concentrated sulfuric acid (95%-98%) and concentrated hydrogen peroxide solution (30%) mixed in a volume ratio of 3:1) for 10 to 30 minutes, then rinse with a large amount of ultra-clean water and blow dry with nitrogen.

[0076] Step 2: Fix the framework nucleic acid nanostructure to the medium plane. Drop a drop of salt solution of adsorption-assisting ions (magnesium ions, calcium ions, nickel ions, etc.) on the plane medium, leave it for 2 minutes, and then drop the framework nucleic acid nanostructure dispersion on the interface. By adding adsorption-assisting ions, the adsorption effect between the negatively charged nucleic acid nanostructure and the interface is enhanced.

[0077] Step 3: Prepare rare earth-framework nucleic acid nanostructures on the interface. The mineralization growth solution is a mixed solution of rare earth ions and counter ions, wherein rare earth chloride is selected as the rare earth ion and Ce:Yb:Er=89:10:1 (molar ratio), and the concentration is 1mmol / L, wherein rare earth chloride forms chloride ions and rare earth ions in the solution, and rare earth ions combine with the phosphate groups of DNA to form rare earth phosphates; the counter ion is magnesium ions, and the concentration is 10mmol / L. Soak the side of the medium with the framework nucleic acid fixed in the mineralization growth solution and incubate at 37℃ for 1 to 7 days. Take out the medium plane, rinse slowly with ultrapure water, dry it, and then characterize it by atomic force microscopy, scanning electron microscopy and other means. Figure 3 This is a transmission electron micrograph of the rare earth-framework nucleic acid nanocomposite material in Example 2. The nanocomposite material completely replicates the structure of the framework nucleic acid tetrahedron, and the Ce, Yb, and Er elements are evenly distributed on the tetrahedron.

[0078] Figure 4 The fluorescence spectrum and polarized fluorescence of the rare earth-nucleic acid nanocomposite material in Example 2 show that the upconversion luminescence intensity of a single particle changes periodically with the change of the emission polarization angle. The dynamic analysis of the spatial orientation of a single particle is achieved by utilizing the highly polarized crystal field transition spectrum, and the new property of single particle polarized fluorescence is obtained.

[0079] In summary, the rare earth-framework nucleic acid nanocomposite material described in the present invention uses framework nucleic acids of different morphologies as templates, so that rare earth elements are connected to the framework nucleic acid structure template through electrostatic interaction and coordination, and then a rare earth mineralization layer is formed through deposition growth, and finally a rare earth-framework nucleic acid nanocomposite material with controllable shape, uniform distribution, biocompatibility, luminescence and catalytic properties is formed, which can be applied to cell-related imaging and treatment. The preparation method described in the present invention realizes the preparation of rare earth-framework nucleic acid nanocomposite materials. Compared with the existing means of synthesizing rare earth nanomaterials (such as traditional solvothermal method, coprecipitation method, thermal decomposition method, etc.), the present invention has a significant breakthrough in the preparation of nano-sized rare earth complex structures.

[0080] The above embodiments are only used to help understand the method and core idea of ​​the present invention. It should be noted that, for those skilled in the art, several improvements and modifications can be made to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the scope of protection of the claims of the present invention.

Claims

1. A method for preparing a rare earth-framework nucleic acid nanocomposite material, characterized in that: comprising step A) and step B), or comprising step A) and step C): A) Preparation of framework nucleic acid nanostructures; B) Interface reaction method: adsorbing the framework nucleic acid nanostructure obtained in step A) on the interface, and then performing rare earth mineralization growth; the interface is selected from silicon wafer, glass wafer or mica wafer; adjusting the type and concentration of auxiliary adsorption ions to fix the framework nucleic acid nanostructure on the interface; the auxiliary adsorption ions include one or more of magnesium ions, calcium ions and nickel ions; then immersing the interface with the fixed framework nucleic acid in a mineralization growth solution, so that the rare earth elements are deposited and grown on the framework nucleic acid template to form the target rare earth-framework nucleic acid nanocomposite material; C) Solution reaction method: the framework nucleic acid nanostructure template obtained in step A) is dispersed in a mineralization growth solution, and rare earth mineralization growth is performed in a solution state; The mineralization growth solution is a mixed solution of rare earth ions and counter ions; The counter ion is selected from magnesium ion; The rare earth ions include Ce ions, Yb ions and Er ions; The molar ratio of the Ce ions, Yb ions and Er ions is 89:10:

1.

2. The method for preparing the rare earth-framework nucleic acid nanocomposite material according to claim 1, characterized in that: The concentration of the framework nucleic acid is 1-100 nmol / L.

3. The method for preparing the rare earth-framework nucleic acid nanocomposite material according to claim 1, characterized in that: The concentration of the rare earth ions is 0.1-50 mmol / L; The concentration of the counter ion is 1-100 mmol / L; The molar ratio of the rare earth ion to the counter ion is (0.001-50):

1.

4. The rare earth-framework nucleic acid nanocomposite material prepared by the preparation method according to any one of claims 1 to 3, characterized in that: It includes a framework nucleic acid and a rare earth mineralization layer deposited on the surface of the framework nucleic acid; The shape of the framework nucleic acid is one or more of a triangle, a square, and a tetrahedron.

5. The rare earth-framework nucleic acid nanocomposite material according to claim 4, characterized in that: The rare earth mineralization layer is selected from one or more of inorganic salts, oxides and hydroxides of rare earth ions.

6. Use of the rare earth-framework nucleic acid nanocomposite material prepared by the preparation method according to any one of claims 1 to 3 or the rare earth-framework nucleic acid nanocomposite material according to any one of claims 4 to 5 in high-resolution single-particle fluorescence imaging.

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