A quantum dot nanoprobe Ag2S@PEG-ABS and its preparation method and application

Abstract

The present invention discloses a quantum dot nanoprobe and its preparation method and application. Ag2S quantum dots are prepared by using monomer 3-mercaptopropionic acid (3-MPA) and silver nitrate, and then a nanotheranostic probe of Ag2S quantum dots modified based on polyethylene glycol (PEG) and 4-(2-aminoethyl)benzenesulfonamide (ABS) is obtained. The preparation process of the present invention is simple, the reaction is mild, and the prepared Ag2S@PEG-ABS quantum dots have small particle size, good water solubility, uniform dispersion and good stability. Moreover, the prepared Ag2S@PEG-ABS quantum dots have both good fluorescence imaging ability in the second near-infrared region and high photothermal conversion performance, and are an ideal multifunctional cancer treatment reagent.

Description

Technical Field

[0001] The present invention relates to the technical field of probes, and particularly relates to a quantum dot nanosensor and its preparation method and application. Background Art

[0002] Malignant tumors have high mortality and high recurrence rates and are still one of the important diseases threatening human health and life. Traditional treatment methods, including radiotherapy, chemotherapy, and local surgical resection, are associated with high recurrence rates, low specificity, severe side effects, and drug resistance. To achieve precise treatment and fewer side effects, phototherapy technology is a promising cancer treatment method because it has specific light-induced diagnosis and targeted cytotoxicity to cancer cells, with high spatio-temporal accuracy and non-invasiveness. In particular, fluorescence imaging (FLI) in the second near-infrared region (NIR-II, 1000-1700 nm) can penetrate deep into tissues with minimal interference and light damage to the tissues. On the other hand, compared with photodynamic therapy (PDT), photothermal therapy (PTT) is highly efficient and non-invasive, and only requires a single administration and a single irradiation to effectively inhibit the photothermal effect of tumors.

[0003] Carbonic anhydrase IX (CAIX) is a hypoxia-induced enzyme that shuttles in cells by producing bicarbonate ions in the extracellular microenvironment and is a survival factor that protects cancer cells from hypoxia and acidosis. Studies have confirmed that CAIX is closely related to the hypoxia level and the expression of hypoxia-inducible factor (HIF-1α). In addition, CAIX is usually overexpressed in cancers but not expressed in normal tissues. Therefore, CAIX has become an important target for the diagnosis and treatment of hypoxic tumors such as osteosarcoma.

[0004] Quantum dots are colloidal semiconductor nanocrystals. As a new type of material, quantum dots have many fluorescence characteristics, including: precisely tunable emission peaks for multi-channel imaging; high photostability to extend the imaging time without losing signals, which is beneficial for fluorescence-guided surgery; large Stokes shifts for multi-color imaging using a single excitation wavelength; wide excitation spectra that are easy to excite to improve sensitivity; fluorescence quantum yields of quantum dots superior to organic dyes in the near-infrared range; longer excited-state lifetimes to avoid autofluorescence of cells and other tissue components; and high specific surface areas for functionalization to create multimodal probes, etc.

[0005] Therefore, it is of great significance to develop and design a CAⅨ-targeted Ag2S quantum dot biosensor integrating diagnostic and therapeutic functions for hypoxia tumor treatment guided by NIR-Ⅱ imaging. Summary of the Invention

[0006] The object of the present invention is to provide a quantum dot nanoprobe and its preparation method and application. The quantum dot nanoprobe of the present invention, due to being modified by PEG and ABS, has good water solubility and stability, can provide good optical signals after effectively targeting tumor sites, and provides a feasible method for in vivo diagnosis of tumors.

[0007] To achieve the above object, the present invention adopts the following technical solutions:

[0008] In the first aspect of the present invention, a quantum dot nanoprobe Ag2S@PEG-ABS is provided, and the structural formula of the quantum dot nanoprobe is as follows:

[0009]

[0010] Among them, the QDs are Ag2S quantum dots, and n is an integer from 20 to 25.

[0011] In the second aspect of the present invention, a preparation method of a quantum dot nanoprobe is provided, and the method includes:

[0012] After degassing ethylene glycol, heat it to 110 - 120 °C, then add 3-MPA and AgNO3, slowly raise the temperature to 150 - 160 °C, carry out a holding reaction, and then obtain Ag2S QDs through purification;

[0013] Add the Ag2S QDs to HS-PEG-COOH and react under nitrogen protection to obtain PEG-modified Ag2S QDs, namely Ag2S@PEG;

[0014] After centrifuging and washing the Ag2S@PEG, disperse it in an aqueous solution, add EDC and NHS, stir for an activation reaction, after the activation reaction ends, add ABS and continue to stir and react, and obtain the quantum dot nanoprobe Ag2S@PEG-ABS through centrifugation and collection.

[0015] Further, the mass ratio of AgNO3 to 3-MPA is 1:13 - 15.

[0016] Further, the mass ratio of Ag2S QDs to HS-PEG-COOH is 1:2 - 4.

[0017] Further, the molar ratio of Ag2S@PEG, EDC, NHS, and ABS is 1:1 - 2:1:1 - 2.

[0018] Further, the time of the holding reaction is 2 - 6 h.

[0019] Further, the reaction time of adding Ag2S QDs and HS-PEG-COOH under nitrogen protection is 12 to 24 h.

[0020] Further, the activation reaction time is 1 to 4 h; the reaction time of adding ABS and continuing stirring is 12 to 24 h.

[0021] In the third aspect of the present invention, there is provided an application of the quantum dot nanoprobe in the preparation of a tumor-targeted NIR-II fluorescence imaging reagent.

[0022] In the fourth aspect of the present invention, there is provided an application of the quantum dot nanoprobe in the preparation of a reagent for inhibiting hypoxic tumor cells and in vivo.

[0023] In the fifth aspect of the present invention, there is provided an application of the quantum dot nanoprobe in pH detection and photodynamic therapy.

[0024] One or more technical solutions in the embodiments of the present invention have at least the following technical effects or advantages:

[0025] In the quantum dot nanoprobe Ag2S@PEG-ABS and its preparation method and application provided by the present invention, it is obtained through ligand exchange between its mercapto group and the quantum dot. The PEG-modified Ag2S quantum dots are purified by centrifugal separation, so that the obtained product has good biocompatibility. Then, ABS is connected through an amide condensation reaction, and it can target tumors by targeting the overexpressed CAⅨ in hypoxic tumors. Compared with the existing inventions, the beneficial effects of the present invention are as follows:

[0026] (1) The preparation method of the present invention is simple and easy to operate, and the synthesis cost is low;

[0027] (2) The data of DLS particle size and zeta potential show that the Ag2S quantum dots modified by PEG and ABS have good water solubility and stability;

[0028] (3) The Ag2S quantum dots modified by PEG and ABS in the present invention have good optical characteristics, and can provide good optical signals after effectively targeting the tumor site, providing a feasible method for in vivo diagnosis of tumors;

[0029] (4) The photothermal data show that the PEG-modified Ag2S quantum dots have excellent photothermal conversion efficiency and photothermal stability, which can provide favorable conditions for photothermal ablation of tumors. Description of the Drawings

[0030] To more clearly illustrate the technical solutions in the embodiments of the present invention, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0031] Figure 1 Schematic flow chart of the preparation method of the quantum dot nanoprobe Ag2S@PEG-ABS provided by the present invention;

[0032] Figure 2 Characterization of the size and morphology of the CAⅨ-targeted Ag2S quantum dot probe of the present invention;

[0033] Figure 3 Polymer dispersity index before and after modification of the CAⅨ-targeted Ag2S quantum dot probe of the present invention

[0034] Figure 4 Second-region fluorescence characterization of the CAⅨ-targeted Ag2S quantum dot probe of the present invention;

[0035] Figure 5 Thermal imaging image of the CAⅨ-targeted Ag2S quantum dot probe of the present invention;

[0036] Figure 6 Sample images after laser irradiation of the CAⅨ-targeted Ag2S quantum dot probe of the present invention before and after modification;

[0037] Figure 7 In vivo imaging of the CAⅨ-targeted Ag2S quantum dots of the present invention in colorectal cancer CT26 tumor-bearing mice;

[0038] Figure 8 Tumor photothermal animal experiment verification of the CAⅨ-targeted Ag2S quantum dots of the present invention;

[0039] Figure 9 Hematoxylin-eosin staining sections of the main organ tissues of mice in different experimental groups. Detailed implementation manners

[0040] The following will specifically describe the present invention in combination with the detailed implementation manners and embodiments, and the advantages and various effects of the present invention will be presented more clearly therefrom. Those skilled in the art should understand that these detailed implementation manners and embodiments are used to illustrate the present invention, rather than to limit the present invention.

[0041] Throughout the specification, unless otherwise specifically stated, the terms used herein shall be construed as having the meanings as commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art to which the present invention pertains. In case of any contradiction, the present specification shall prevail.

[0042] Unless otherwise specifically stated, various raw materials, reagents, instruments, equipment, etc. used in the present invention can be obtained through market purchase or by existing methods.

[0043] An embodiment of the present invention provides a quantum dot nanoprobe, and the general idea is as follows:

[0044] According to a typical embodiment of the present invention, a quantum dot nanoprobe Ag2S@PEG-ABS is provided, and the structural formula of the quantum dot nanoprobe is as follows:

[0045]

[0046] Wherein, the QDs are Ag2S quantum dots, and the n is an integer of 20-25.

[0047] According to a typical embodiment of the present invention, a preparation method of a quantum dot nanoprobe is provided, and its synthesis route is as shown in the figure:

[0048]

[0049] As a specific embodiment, the method specifically includes the following steps:

[0050] (1) Add 10 mL of ethylene glycol into a 25 mL three-necked round-bottom flask and degas for 30 minutes. After degassing, heat the ethylene glycol to 110-120 °C, then add 100-200 μL of 3-MPA to the reaction system, and subsequently quickly add 0.006-0.01 g of AgNO3. Slowly raise the temperature to 150-160 °C. After the temperature is raised, the reaction system begins to change from a milky white turbid state to a light yellow clear state, and then to brown and finally to dark brown. Maintain the above temperature and continue vigorous mechanical stirring for 2-6 hours, and then stop the reaction. Centrifuge the product, discard the supernatant ethylene glycol, redisperse the obtained precipitate in an aqueous solution, wash it 3 times with a 30 kDa ultrafiltration centrifugal tube, collect the reaction product Ag2S QDs after washing, and store it in a 4 °C refrigerator for subsequent synthesis and performance determination.

[0051] (2) To the aqueous solution of the product Ag2S QDs obtained in step 1) (5 mL, 10 mM Ag +Add 20 - 40 μmol of HS-PEG-COOH (MW = 1000) to it, and react for 12 - 24 h under nitrogen protection to obtain PEG-modified Ag2S QDs, that is, the product Ag2S@PEG. Centrifuge and wash Ag2S@PEG three times, and store it in a refrigerator at 4 °C.

[0052] (3) After centrifuging and washing the obtained product Ag2S@PEG three times, redisperse it in an aqueous solution. Add 50 - 70 μmol of EDC and 80 - 100 μmol of NHS to the Ag2S@PEG solution, and stir slowly for 1 - 4 h to activate the carboxyl groups on PEG. After the activation is completed, add 50 - 80 μmol of ABS to the above mixed system, and continue to stir and react for 12 - 24 h. Finally, centrifuge using an ultrafiltration centrifuge tube, discard the excess reactants, and collect Ag2S@PEG-ABS. Store the product in a refrigerator at 4 °C.

[0053] Next, a quantum dot nanoprobe of the present application, its preparation method and application will be described in detail with reference to examples and experimental data.

[0054] Example 1: Quantum dot nanoprobe Ag2S@PEG-ABS and its preparation method

[0055] (1) Add 10 mL of ethylene glycol to a 25 mL three-necked round-bottom flask and degas for 30 minutes. After degassing, heat the ethylene glycol to 115 °C, then add 150 μL of 3-MPA to the reaction system, and then quickly add 0.008 g of AgNO3. Slowly raise the temperature to 155 °C. After the temperature is raised, the reaction system begins to change from a milky white turbid state to a light yellow clear state, and then to brown and finally to dark brown. Keep the above temperature and continue vigorous mechanical stirring for 4 hours, then stop the reaction. Centrifuge the product, discard the supernatant ethylene glycol, redisperse the obtained precipitate in an aqueous solution, wash it three times with a 30 kDa ultrafiltration centrifuge tube, collect the reaction product Ag2S QDs after washing, and store it in a refrigerator at 4 °C for subsequent synthesis and performance measurement.

[0056] (2) Add 30 μmol of HS-PEG-COOH (MW = 1000) to the aqueous solution of the product Ag2S QDs obtained in step 1) (5 mL, 10 mM Ag + ) and react for 18 h under nitrogen protection to obtain PEG-modified Ag2S QDs, that is, the product Ag2S@PEG. Centrifuge and wash Ag2S@PEG three times, and store it in a refrigerator at 4 °C.

[0057] (3) After centrifuging and washing the obtained product Ag2S@PEG three times, redisperse it in an aqueous solution. Add 60 μmol of EDC and 90 μmol of NHS to the Ag2S@PEG solution, and stir slowly for 2 h to activate the carboxyl groups on PEG. After the activation is completed, add 65 μmol of ABS to the above mixed system, and continue stirring and reacting for 18 h. Finally, centrifuge using an ultrafiltration centrifuge tube, discard the excess reactants, and collect Ag2S@PEG-ABS. Store the product in a refrigerator at 4 °C.

[0058] Example 2: Quantum dot nanoprobe Ag2S@PEG-ABS and its preparation method

[0059] (1) Add 10 mL of ethylene glycol to a 25 mL three-necked round-bottom flask and degas for 30 minutes. After degassing, heat the ethylene glycol to 110 °C, then add 100 μL of 3-MPA to the reaction system, and subsequently quickly add 0.006 g of AgNO3. Slowly raise the temperature to 150 °C. After the temperature is raised, the reaction system starts to change from a milky white turbid state to a light yellow clear state, and then turns brown and finally dark brown. Maintain the above temperature and continue vigorous mechanical stirring for 2 hours, then stop the reaction. Centrifuge the product, discard the supernatant ethylene glycol, redisperse the obtained precipitate in an aqueous solution, wash it three times with a 30 kDa ultrafiltration centrifuge tube, and collect the reaction product Ag2S QDs after washing. Store it in a refrigerator at 4 °C for subsequent synthesis and performance determination.

[0060] (2) Add 30 μmol of HS-PEG-COOH (MW = 1000) to the aqueous solution of the product Ag2S QDs obtained in step (1) (5 mL, 10 mM Ag + ) and react for 12 h under nitrogen protection to obtain PEG-modified Ag2S QDs, that is, the product Ag2S@PEG. Centrifuge and wash Ag2S@PEG three times and store it in a refrigerator at 4 °C.

[0061] (3) After centrifuging and washing the obtained product Ag2S@PEG three times, redisperse it in an aqueous solution. Add 50 μmol of EDC and 80 μmol of NHS to the Ag2S@PEG solution, and stir slowly for 1 h to activate the carboxyl groups on PEG. After the activation is completed, add 50 μmol of ABS to the above mixed system, and continue stirring and reacting for 12 h. Finally, centrifuge using an ultrafiltration centrifuge tube, discard the excess reactants, and collect Ag2S@PEG-ABS. Store the product in a refrigerator at 4 °C.

[0062] Example 3: Quantum dot nanoprobe Ag2S@PEG-ABS and its preparation method

[0063] (1) Add 10 mL of ethylene glycol into a 25 mL three-necked round-bottom flask and degas for 30 minutes. After degassing, heat the ethylene glycol to 120 °C, then add 200 μL of 3-MPA to the reaction system, and subsequently quickly add 0.01 g of AgNO3. Slowly raise the temperature to 160 °C. After the temperature is raised, the reaction system begins to change from a milky white turbid state to a light yellow clear state, and then turns brown and finally dark brown. Maintain the above temperature and continue vigorous mechanical stirring for 6 hours, then stop the reaction. Centrifuge the product, discard the supernatant ethylene glycol, redisperse the obtained precipitate in an aqueous solution, wash it 3 times with a 30 kDa ultrafiltration centrifugal tube. After washing, collect the reaction product Ag2S QDs, and store it in a refrigerator at 4 °C for subsequent synthesis and performance measurement.

[0064] (2) Add 40 μmol of HS-PEG-COOH (MW = 1000) to the aqueous solution (5 mL, 10 mM Ag + ) of the product Ag2S QDs obtained in step (1). React under nitrogen protection for 24 h to obtain PEG-modified Ag2S QDs, that is, the product Ag2S@PEG. Centrifuge and wash Ag2S@PEG 3 times, and store it in a refrigerator at 4 °C.

[0065] (3) After centrifuging and washing the obtained product Ag2S@PEG 3 times, redisperse it in an aqueous solution. Add 70 μmol of EDC and 100 μmol of NHS to the Ag2S@PEG solution, and stir slowly for 4 h to activate the carboxyl groups on PEG. After the activation is completed, add 80 μmol of ABS to the above mixed system, and continue stirring and reacting for 24 h. Finally, centrifuge using an ultrafiltration centrifugal tube, discard the excess reactants and collect Ag2S@PEG-ABS. Store the product in a refrigerator at 4 °C.

[0066] Experimental Example 1. Performance Measurement of Quantum Dot Nanoprobe Ag2S@PEG-ABS

[0067] 1. Characterization of Quantum Dot Nanoprobe Ag2S@PEG-ABS

[0068] The morphology of the quantum dot sample in Example 1 was observed by transmission electron microscopy (TEM) using Hitachi TEM (HT7700, Japan). The hydrodynamic diameter and polymer dispersion index of the quantum dot nanoprobe Ag2S@PEG-ABS were measured by Malvern Zetasizer Nano series ZS-90.

[0069] The results are as Figure 2As shown, it can be seen that the synthesized quantum dots are spherical with a diameter of about 100nm. DLS data show that the average particle size of the synthesized silver sulfide quantum dots is 141.5nm, and the average particle sizes of Ag2S@PEG and Ag2S@PEG-ABS are 188.7nm and 229.5nm, respectively, indicating the successful synthesis of quantum dots and nanoprobe Ag2S@PEG-ABS.

[0070] The results are as follows Figure 3 As shown, it can be seen that the PDI values of the synthesized quantum dots and probe Ag2S@PEG-ABS were measured to be 0.326 and 0.195, respectively, indicating that after modification of PEG and ABS, the water solubility of the probe was greatly improved.

[0071] 2. Second-zone fluorescence characterization of quantum dot nanoprobe Ag2S@PEG-ABS

[0072] The Ag2S quantum dots were accurately weighed with a 1 / 10,000 analytical balance and prepared into a 1 mg / mL solution for use. The solution was diluted to a 0.1 mg / mL working solution during testing, and the near-infrared zone II fluorescence emission of the quantum dots and probes synthesized in Example 1 was detected with a near-infrared zone II imager.

[0073] The results are as follows Figure 4 As shown, it can be seen that the synthesized quantum dots and probe Ag2S@PEG-ABS have strong fluorescence above 1000nm in the near-infrared region II, and can be used for subsequent in vivo near-infrared region II imaging.

[0074] 3. Photothermal effect of quantum dot nanoprobe Ag2S@PEG-ABS

[0075] Prepare Ag2S@PEG-ABS into a 1 mg / mL stock solution with water for later use. Take a certain amount of mother solution from each of the above storage solutions and add water to prepare a 0.1 mg / mL sample working solution, which is then added to the cuvettes. Place the cuvette containing the test solution at 808 nm and 1.5 W / cm 2 The samples were irradiated with near-infrared laser for 5 minutes and the temperature changes were recorded every 10 seconds.

[0076] The results are as follows Figure 5 As shown, it can be seen that the photothermal effect of the probe is concentration-dependent. As the concentration increases, the maximum equilibrium temperature increases. At 1 mg / mL, the equilibrium temperature can reach 61.4°C.

[0077] The results are as follows Figure 6 As shown, it can be seen that Ag2S quantum dots precipitate after five minutes of laser irradiation, while the Ag2S@PEG-ABS probe remains stable after three cycles of irradiation, cooling and re-irradiation, indicating that the photothermal stability of the probe is greatly improved after modification with PEG and ABS.

[0078] It should be noted that the performance of the quantum dot nanoprobes prepared in Examples 2-3 is basically the same as that of the quantum dot nanoprobes in Example 1, and will not be elaborated here.

[0079] Experimental Example 2. In vivo research experiment

[0080] 1. Tumor targeting ability of near-infrared CAⅨ-targeted Ag2S quantum dots

[0081] A subcutaneous tumor-bearing model of Balb / c mice (male) was established using CT26 cells. Near-infrared CAⅨ-targeted Ag2S quantum dots were administered via the tail vein, and real-time near-infrared fluorescence imaging was performed using a small animal in vivo imaging system to observe the metabolic distribution of the compound in the mice at different time points.

[0082] The results are as Figure 7 shown. It can be seen that Ag2S@PEG-ABS effectively targets tumors in mice and has the highest enrichment level 6 hours after injection.

[0083] 2. Tumor phototherapy application of near-infrared CAⅨ-targeted Ag2S quantum dots in tumor-bearing mice

[0084] A subcutaneous tumor-bearing model of Balb / c male mice was established using CT26 cells and divided into (1) PBS group, (2) group administered with the quantum dot nanoprobe of Example 1 alone, (3) PBS + Laser group, and (4) group administered with the quantum dot nanoprobe of Example 1 + Laser group, with 5 mice in each group. Administration was via the tail vein. 24 hours later, only groups (2) and (4) were irradiated with 808 nm laser at 1.5 W / cm 2 for 5 minutes, and the body weight and tumor volume changes of the above 4 groups of mice were continuously observed and measured.

[0085] The results are as Figure 8 shown. It can be seen that the growth inhibition effect has been achieved in the Ag2S@PEG-ABS + laser group after 6 - 8 days, while the tumors are still proliferating in other experimental groups. The body weights of the tumor-bearing mice in different treatment groups all increased during the treatment, indicating that Ag2S@PEG-ABS has good biocompatibility. Finally, the tumor inhibition rate was calculated. The tumor inhibition rate of the Ag2S@PEG-ABS + Laser group was 91.5%, with the best inhibitory effect.

[0086] 3. Hematoxylin-eosin staining sections of the main organ tissues of mice in different experimental groups.

[0087] After the mice in the PBS group and the other 3 experimental groups were sacrificed, the heart, liver, spleen, lungs, and kidneys were collected and fixed in 4% paraformaldehyde. Then, paraffin embedding, sectioning, and hematoxylin and eosin (H&E) staining were performed according to the standard procedures.

[0088] The results are as Figure 9 shown. It can be seen that compared with the two groups treated with PBS, there is no obvious inflammatory damage or tissue damage in the two groups treated with Ag2S@PEG-ABS, indicating that the bioprobe has good biocompatibility in vivo.

[0089] Finally, it should also be noted that the term "comprising", "including" or any other variant thereof is intended to cover non-exclusive inclusion, so that a process, method, article or device comprising a series of elements not only includes those elements but also includes other elements not expressly listed, or further includes elements inherent to such process, method, article or device.

[0090] Although the preferred embodiments of the present invention have been described, those skilled in the art can make additional changes and modifications once they learn the basic creative concept. Therefore, the appended claims are intended to be construed as including the preferred embodiments as well as all changes and modifications falling within the scope of the present invention.

[0091] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, the present invention is also intended to include these modifications and variations.

Claims

1. A quantum dot nanoprobe Ag2S@PEG-ABS, characterized in that, The structural formula of the quantum dot nanoprobe is as follows: Among them, the QDs are Ag2S quantum dots, and the n is an integer from 20 to 25.

2. The preparation method of the quantum dot nanoprobe Ag2S@PEG-ABS according to claim 1, characterized in that, The method includes: After degassing ethylene glycol and heating it to 110 - 120 °C, add 3-MPA and AgNO3, slowly raise the temperature to 150 - 160 °C, then carry out a holding reaction, and after purification, obtain Ag2S QDs; Add the Ag2S QDs to HS-PEG-COOH and react under nitrogen protection to obtain PEG-modified Ag2S QDs, namely Ag2S@PEG; After centrifuging and washing the Ag2S@PEG, disperse it in an aqueous solution, add EDC and NHS, stir for an activation reaction, after the activation reaction ends, add ABS and continue to stir and react, after centrifuging and collecting, obtain the quantum dot nanoprobe Ag2S@PEG-ABS.

3. The preparation method of a quantum dot nanoprobe according to claim 2, wherein The mass ratio of the AgNO3 to the 3-MPA is 1:13 - 15.

4. The preparation method of a quantum dot nanoprobe according to claim 2, characterized in that, The mass ratio of the Ag2S QDs to the HS-PEG-COOH is 1:2 - 4.

5. The preparation method of a quantum dot nanoprobe according to claim 2, characterized in that, The molar ratio of the Ag2S@PEG, the EDC, NHS, and the ABS is 1:1 - 2:1:1 - 2.

6. The preparation method of a quantum dot nanoprobe according to claim 2, characterized in that, The time of the holding reaction is 2 - 6 h.

7. The preparation method of a quantum dot nanosensor according to claim 2, characterized in that, The time for adding the Ag2S QDs to HS-PEG-COOH and reacting under nitrogen protection is 12 - 24 h.

8. The preparation method of a quantum dot nanoprobe according to claim 2, characterized in that The time of the activation reaction is 1 - 4 h; the time for adding ABS and continuing to stir and react is 12 - 24 h.

9. Use of the quantum dot nanoprobe according to claim 1 in the preparation of a tumor-targeted NIR-II fluorescence imaging reagent.

10. Use of the quantum dot nanoprobe according to claim 1 in the preparation of a drug for treating tumors by phototherapy.

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