Sugar azide nanoparticles as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of tumor biological imaging, and particularly relates to azide sugar nanoparticles as well as a preparation method and application thereof. In particular to application of polyethylene glycol-block-polylactic acid combined with tetraacetyl-2-amino-2-deoxy-2-azido-mannose in preparation of a tumor specific imaging agent, a preparation method of the azido sugar nanoparticles and the prepared azido sugar nanoparticles. The invention also provides an application of the azide sugar nanoparticle in preparation of a solid tumor specific imaging agent. The invention provides a novel tumor biological imaging method with high specificity and high sensitivity through combination of the azido sugar nanoparticles and a biological orthogonal chemical reaction, and provides important technical support for early diagnosis and treatment of tumors.

Description

Technical Field

[0001] The present invention belongs to the technical field of tumor bioimaging, and in particular relates to azidosugar nanoparticles and a preparation method and application thereof. Background Art

[0002] Existing tumor bio-imaging technologies play an important role in the early diagnosis, progression monitoring and treatment effect evaluation of cancer, but they also face many challenges and limitations. First, most traditional imaging agents have low specificity in the body and often accumulate nonspecifically in normal tissues, resulting in high background noise, which affects the accurate identification of tumor tissues. Secondly, traditional imaging agents have limited penetration ability, especially when dealing with solid tumors, and it is often difficult to effectively pass through the vascular barrier and enter deep into the tumor tissue. In addition, due to insufficient accumulation of imaging agents in tumor tissues, it is often difficult to achieve effective imaging of early tumors.

[0003] At present, although traditional tumor imaging technologies such as radioisotope markers, fluorescent dyes and superparamagnetic nanoparticles have achieved certain success in certain applications, they still have shortcomings in tumor specificity, tissue penetration depth and imaging sensitivity. Summary of the invention

[0004] In view of the above problems, the present invention provides azidosugar nanoparticles and preparation methods and applications thereof, mainly to solve the problems that current tumor bioimaging still has deficiencies in tumor specificity, tissue penetration depth and imaging sensitivity.

[0005] In order to solve the above problems, the present invention adopts the following technical solutions:

[0006] The first aspect of the present invention provides the use of tetraacetyl-2-amino-2-deoxy-2-azido-mannose in the preparation of a tumor-specific imaging agent; wherein the tetraacetyl-2-amino-2-deoxy-2-azido-mannose is used to enhance the sensitivity and specificity of the tumor-specific imaging agent for tumor imaging.

[0007] Polyethylene glycol-block-polylactic acid (PEG5k-b-PLA8k) is modified by tetraacetyl-2-amino-2-deoxy-2-azido-mannose (Ac4ManNAz). One of them is an encapsulation carrier and the other is an encapsulated drug. They work synergistically to form nanoparticles that can be delivered to the local tumor, providing sensitivity and specificity for tumor imaging. It should be noted that the molecular weight of PEG in PEG5k-b-PLA8k (polyethylene glycol 5k-block-polylactic acid 8k) is 5k, and the molecular weight of PLA is 8k.

[0008] The second aspect of the present invention provides the use of polyethylene glycol-block-polylactic acid combined with tetraacetyl-2-amino-2-deoxy-2-azido-mannose in the preparation of a tumor-specific imaging agent; wherein the polyethylene glycol-block-polylactic acid is PEG5k-b-PLA8k. One of the two is an encapsulation carrier and the other is an encapsulated drug, and the combination forms nanoparticles, which significantly improve the imaging effect, especially the specificity and sensitivity.

[0009] The third aspect of the present invention provides a method for preparing azidosugar nanoparticles and the prepared azidosugar nanoparticles.

[0010] The preparation method of azidosugar nanoparticles comprises the following steps:

[0011] S1, dissolving polyethylene glycol-block-polylactic acid and tetraacetyl-2-amino-2-deoxy-2-azido-mannose in dimethyl sulfoxide, and slowly adding the resulting solution into ultrapure water;

[0012] S2. The dialyzed liquid is collected and freeze-dried to obtain azidosugar nanoparticle powder.

[0013] In the preparation process, some of the process conditions may specifically adopt any one or more of the following schemes, but are not limited thereto:

[0014] In one of them, in step S1, polyethylene glycol-block-polylactic acid and tetraacetyl-2-amino-2-deoxy-2-azido-mannose are added to dimethyl sulfoxide in a ratio of 4:1 to 10:1 and fully stirred; the concentration of dimethyl sulfoxide is 10±0.5 mg / mL.

[0015] In the second one, in step S1, a solution formed by dissolving polyethylene glycol-block-polylactic acid and tetraacetyl-2-amino-2-deoxy-2-azido-mannose in dimethyl sulfoxide is added dropwise into ultrapure water. Ultrapure water is a general definition, which mainly means that water with very few impurities is required, and the order of magnitude of its purity is not strictly required, as long as it can normally prepare azidosugar nanoparticles and maintain the performance.

[0016] Thirdly, in step S1, the molecular weight of polyethylene glycol in polyethylene glycol-block-polylactic acid is 5k, and the molecular weight of polylactic acid is 8k; in step S2, dialysis is performed using a dialysis bag of 2000-14000Da and ultrapure water.

[0017] The azidosugar nanoparticles are prepared by any of the aforementioned methods. When characterized, the various indicators are generally shown as a particle size of about 100 nm, a negative charge on the surface, and a PDI of less than 0.3, but are not limited thereto. Particles having similar functions to the present invention formed by combining polyethylene glycol-block-polylactic acid and tetraacetyl-2-amino-2-deoxy-2-azido-mannose should all be within the scope of the present invention.

[0018] The fourth aspect of the present invention provides the use of any of the aforementioned azidosugar nanoparticles in the preparation of a solid tumor-specific imaging agent. It can effectively penetrate the vascular barrier into the deep of the tumor tissue, increase the degree of accumulation in the tumor tissue, and thus achieve effective presentation of early tumors. And the formed tumor-specific imaging agent has extremely high specificity and sensitivity. The imaging signal intensity of the tumor-specific imaging agent at the tumor site is significantly stronger than that of the internal organs, and it can react with the fluorescent probe or nuclide in a relatively short time and dynamically image. Through dynamic imaging, the distribution of the imaging agent in the body can be observed to understand the tumor's uptake and excretion rate of the imaging agent.

[0019] Azidosugar nanoparticles will have a higher intensity of bioorthogonal reaction in tumors, which will help the accumulation of fluorescent probes in the next step. Although azidosugar nanoparticles also have bioorthogonal reactions in other organs, interference can be eliminated through quantitative analysis. And because the intensity of bioorthogonal reaction of azidosugar nanoparticles in tumors is significantly higher than that in other organs, it is also easy to eliminate interference through quantitative analysis.

[0020] In the application process, some of the conditions may be implemented by any one or more of the following solutions, but are not limited thereto:

[0021] In one of them, the tumor-specific imaging agent is a lymphoma-specific imaging agent, which can specifically image lymphoma and facilitate the confirmation of tumor location.

[0022] Second, tumor-specific imaging agents also include fluorescein or radionuclide probes modified with dibenzocyclooctyne, such as DBCO-Cy5 and DBCO-biotin. The DBCO-modified fluorescein or radionuclide probes undergo click chemistry reactions with the azide groups displayed on the surface of tumor cells, thereby achieving efficient tumor-specific imaging.

[0023] Among them, the tumor-specific imaging agent is an injectable preparation. And it can be injected intravenously. Azide sugar nanoparticles have good blood compatibility. After intravenous injection, they can be transmitted to the whole body through blood vessels without toxic side effects.

[0024] Fourthly, the effective concentration of azidosugar nanoparticles is 5-100 μg / ml, and of course 100-2000 μg / ml should also be within the scope of the present invention. At the same time, other concentrations that are different from this concentration range but have similar effects should also fall within the scope of the present invention.

[0025] In the fifth of them, the azidosugar nanoparticles and the fluorescein or radionuclide probe modified with dibenzocyclooctyne are combined, wherein the azidosugar nanoparticles are first injected and the fluorescein or radionuclide probe modified with dibenzocyclooctyne is second injected.

[0026] Among them, the six, the fluorescein or radionuclide probe modified with dibenzocyclooctyne, can generally be imaged normally within 15 to 30 minutes after injection.

[0027] Among them, a fluorescent or radionuclide probe (such as DBCO-Cy5) modified with dibenzocyclooctyne is usually injected 3 to 6 hours after the injection of azidosugar nanoparticles.

[0028] The fifth aspect of the present invention provides a lymphoma-specific imaging agent, which includes any of the aforementioned azidosugar nanoparticles and a fluorescein or radionuclide probe modified with dibenzocyclooctyne. The azidosugar nanoparticles are injected first, and the fluorescein or radionuclide probe modified with dibenzocyclooctyne is injected later, and the specific imaging of the tumor tissue is achieved through a click chemistry reaction. Similarly, it can effectively pass through the vascular barrier and enter deep into the tumor tissue, thereby increasing the degree of accumulation in the tumor tissue, and thus achieving effective presentation of early tumors. And the lymphoma-specific imaging agent has extremely high specificity and sensitivity, and the imaging signal intensity of the tumor-specific imaging agent at the tumor site is significantly stronger than that of the internal organs, and it can react with the fluorescent probe or radionuclide and dynamically image in a relatively short time.

[0029] It can also be considered that the combination of azidosugar nanoparticles and dibenzocyclooctyne-modified fluorescein or radionuclide probes has a certain synergistic effect on tumor imaging, and the combination of the two significantly improves the effect. For example, injecting azidosugar nanoparticles in advance and then injecting DBCO-Cy5 labeling for 30 minutes or even 15 minutes can quickly perform dynamic imaging of the tumor. The combination of the two greatly improves the sensitivity of imaging. Generally, DBCO-Cy5 is injected 3 to 6 hours after the injection of azidosugar nanoparticles.

[0030] The present invention provides a new imaging agent and a new method for tumor bioimaging with high specificity and high sensitivity through the combination of azidosugar nanoparticles and bioorthogonal chemical reactions, and has extremely high specificity and sensitivity, providing important technical support for the early diagnosis and treatment of tumors. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1Characterization of azidosugar nanoparticles. (A) Tyndall effect of AZ-NPs aqueous solution under laser irradiation; (B) Particle size distribution and electron microscope image of AZ-NPs; (C) to (E) Particle size, Zeta potential and PDI of AZ-NPs; (F) to (H) Dynamic changes in particle size of AZ-NPs in PBS, RMPI1640 and PBS+10% FBS within 7 days; (I) Dynamic changes in Zeta potential of AZ-NPs in PBS within 7 days.

[0032] Figure 2 The blood compatibility of AZ-NPs was evaluated.

[0033] Figure 3 To verify the establishment of bioorthogonal reaction of AZ-NPs at the cell level. (A)~(B) Validation of the dose-dependent and time-dependent bioorthogonal level of Raw264.7; (C)~(D) Validation of the dose-dependent and time-dependent bioorthogonal level of THP-1.

[0034] Figure 4 Biodistribution of AZ-NPs in tumor-bearing mice. (A) Dynamic biodistribution of DIR-NPs and free DIR in a living mouse model; (B) Biodistribution of DIR-NPs and free DIR in the heart, liver, spleen, lung, kidney and tumor; (C) Quantitative analysis of tumor signals in (A); (D) Quantitative analysis of signals in each tissue in (B).

[0035] Figure 5 The bioorthogonal effects of AZ-NPs in tumor-bearing mice. (A) Schematic diagram of drug administration to A20 subcutaneous lymphoma mice; (B) Western blotting to verify the level of metabolic modification of azidosugar in the heart, liver, spleen, lung, kidney and tumor of each group; (C) Western blotting to verify the level of metabolic modification of azidosugar in tumor tissue of each group; (D) Tissue immunofluorescence to further detect the level of metabolic modification of azidosugar in tumor tissue of each group.

[0036] Figure 6 AZ-NPs-mediated near-infrared imaging of subcutaneous lymphoma. (A) Dynamic imaging of mice in the AZ-NPs, free AZ, and PBS groups after injection of DBCO-Cy5 fluorescent probe via tail vein; (B) Quantitative analysis of tumor signals in (A); (C) Biodistribution of DBCO-Cy5 in the heart, liver, spleen, lung, kidney, and tumor of mice in each group; (D) Quantitative analysis of signals in each tissue in (C).

[0037] In the figure: * indicates that the p value is less than 0.05, ** indicates that the p value is less than 0.01, *** indicates that the p value is less than 0.001, and **** indicates that the p value is less than 0.0001. The smaller the p value, the more significant the difference. DETAILED DESCRIPTION

[0038] The present invention will be further described below in conjunction with the accompanying drawings.

[0039] The present invention proposes a new strategy for tumor-specific imaging based on bioorthogonal click chemistry reaction, using azidosugar nanoparticles to achieve efficient labeling and precise imaging of tumor tissue. Compared with the prior art, the present invention has made technical improvements in many aspects, significantly improving the specificity and sensitivity of tumor bioimaging.

[0040] First, by utilizing the EPR effect of azidosugar nanoparticles, the accumulation of imaging agents in tumor tissues is enhanced; this mechanism ensures that imaging agents accumulate at high concentrations in the tumor site, thereby improving the labeling efficiency of tumor tissues and reducing nonspecific background signals that may be generated during the imaging process. Secondly, through the metabolic pathway of tumor cells, the azide groups are displayed on the surface of tumor cells to form "artificial ligands", which provide a basis for subsequent specific click chemistry reactions; this design enables the imaging process to more accurately locate tumor tissues and significantly improves the imaging agent's specific recognition ability for tumor cells. In addition, DBCO-modified fluorescein or radionuclide probes are used to undergo click chemistry reactions with azide groups displayed on the surface of tumor cells, achieving efficient tumor-specific imaging; this reaction has a high degree of chemical selectivity and can be completed quickly under physiological conditions without interference from other biological molecules in the body, ensuring the accuracy and efficiency of the imaging process.

[0041] Through the above technical improvements, the present invention successfully improves the sensitivity and specificity of tumor imaging, so that clearer and more accurate imaging effects can be obtained in the early diagnosis and monitoring of tumors, thereby providing more powerful support for clinical cancer treatment.

[0042] Experimental content and results

[0043] 1. Preparation of Azidosugar Nanoparticles

[0044] Azidosugar nanoparticles (AZ-NPs) were prepared by nanoprecipitation. Polyethylene glycol-block-polylactic acid (PEG5k-b-PLA8k) and tetraacetyl-2-amino-2-deoxy-2-azido-mannose (Ac4ManNAz) were dissolved in dimethyl sulfoxide (10.0 mg / mL) at a ratio of 4:1 and added dropwise to ultrapure water under vigorous stirring. After 20 minutes, the mixture was placed in a 14000Da dialysis bag and dialyzed with ultrapure water overnight. The dialyzed solution was collected and freeze-dried to obtain azidosugar nanoparticle powder.

[0045] The molecular structure of PEG5k-b-PLA8k is shown below:

[0046]

[0047] Among them, the molecular weight of PEG is 5k and the molecular weight of PLA is 8k.

[0048] 2. Characterization of Azidosugar Nanoparticles

[0049] A certain concentration of AZ-NPs aqueous solution was prepared, and its particle size distribution and Zeta potential were detected by laser particle size analyzer, respectively. The above nanoparticle dispersion was placed in PBS, 10% FBS, and RMPI1640 at 37°C for 7 days, respectively, to monitor the particle size change of mAb-TPCA-1@HCNPs. A drop of AZ-NPs solution was dropped onto the copper grid and air-dried at room temperature, followed by negative staining with 0.2% (w / w) phosphotungstic acid solution for 60s, and its morphology was observed by TEM.

[0050] like Figure 1 As shown: The particle size of AZ-NPs is about 100nm ( Figure 1 A~C), and the surface carries a negative charge ( Figure 1 D), PDI is less than 0.3 ( Figure 1 E), stable in PBS, RMPI1640 and PBS + 10% FBS ( Figure 1 (F~I).

[0051] 3. Blood compatibility assessment

[0052] Prepare 1 ml of PBS and 1% TritonX-100 solution in advance. At the same time, use PBS as the solvent to prepare a series of equal volume (1 ml) gradient concentration (5 μg / ml, 10 μg / ml, 25 μg / ml, 50 μg / ml, 100 μg / ml, 250 μg / ml, 500 μg / ml, 1000 μg / ml, 2000 μg / ml) AZ-NPs solutions.

[0053] The peripheral blood of Bal / bc mice was collected by eye removal, collected in anticoagulant tubes, and washed slowly with PBS in a clean bench. The movements should be gentle, and then centrifuged at a low speed of 1500rpm / min*10min until the supernatant is clear and transparent, and then the red blood cell sediment was aspirated and slightly shaken to obtain a uniformly dispersed red blood cell suspension. An equal volume of red blood cell suspension was added to the above-prepared solution, and then fully shaken in a 37℃ desktop constant temperature oscillator at a speed of 300rpm / min for 2h, the sample was taken out and centrifuged (1500rpm, 10min), photographed, and finally the supernatant was aspirated and the hemoglobin absorbance OD value was detected by an enzyme marker. The group with 1% Triton X-100 solution was used as a positive control, and the PBS group was used as a negative control. Three replicate wells were set for each sample, and the detection wavelength was 541nm. According to the OD value, the red blood cell hemolysis rate (HR, Hemolysis ratio) was calculated, and the calculation formula is:

[0054]

[0055] Among them, ODt is the OD value of each experimental group, ODn is the OD value of the PBS negative control group, and ODp is the OD value of the 1% Triton X-100 solution positive control group.

[0056] like Figure 2 As shown: the hemolysis rate basically remained at 0% at a concentration of 5-100 μg / ml, and even at the highest concentration of 2000 μg / ml, the hemolysis rate was still less than 10%, proving that AZ-NPs have good blood compatibility and will not cause red blood cell hemolysis. Even at the highest concentration, only a very small amount of red blood cells are lysed.

[0057] 4. Bioorthogonal reaction verification of AZ-NPs

[0058] Raw264.7 and THP-1 were pre-planted in T25 culture flasks until the cells entered the logarithmic growth phase. For dose-dependent studies, 0, 50, 100, and 200 μg / ml of AZ-NPs were added and incubated in a 37°C incubator for 48 h. For time-dependent studies, 50 μg / ml AZ-NPs were added and cells were collected after 0, 24, 48, and 72 h. Protein was then extracted and quantified by the BCA method. The protein was quantified at 5 mg / ml, and then 20 μl of protein was reacted with 2 μl of 10 μM DBCO-biotin at room temperature for 12 h, and then SDS loading buffer was added, boiled at 95°C for 10 min, electrophoresed with 10% SDS-PAGE (100 V, 90 min), transferred to the membrane, and blocked with 5% skim milk at room temperature for 1 h, washed with TBST 3 times, and the PVDF membrane was incubated with streptavidin-horseradish peroxidase (Streptavidin-HRP) in TBST at 4°C for 12 h, washed with TBST 3 times, and finally ECL luminescent liquid was added for exposure, and images were collected by a gel imaging system.

[0059] like Figure 3 As shown in the figure: Whether in Raw264.7 or THP-1 cell lines, as the concentration of AZ-NPs increases and the time prolongs, the imprinted signal gradually increases, indicating that the bioorthogonal reaction mediated by AZ-NPs is concentration-dependent and time-dependent, and the bioorthogonal level gradually increases with increasing dose and prolonging incubation time.

[0060] 5. In vivo biodistribution study of AZ-NPs

[0061] DIR-NPs were prepared by nanoprecipitation method using DIR iodide instead of AZ to investigate the biodistribution of DIR-NPs in a mouse lymphoma model. Female Balb / c mice aged 6 to 8 weeks were selected and fed in an SPF barrier environment for one week. Then, 1*10 7 A20 cells, and wait until the tumor grows to 50-100 mm 3 DIR-NPs were injected into the tail vein, and a control group was injected with free DIR. Then, tumor signals were dynamically monitored by in vivo imaging of small animals.

[0062] like Figure 4 As shown in: In vivo imaging data of small animals at multiple time points showed that the signal intensity of the local tumor in the DIR-NPs group was significantly higher than that in the free DIR group ( Figure 4In addition, the in vitro organ imaging of various organs also further demonstrated the high accumulation of DIR-NPs in tumors. It is worth noting that free DIR has almost no aggregation in tumors, but DIR-NPs have a very high aggregation degree. The aggregation of the two in tumor sites has a very significant difference ( Figure 4 (B, D).

[0063] 6. In vivo bioorthogonal studies of AZ-NPs

[0064] A20 tumor-bearing mice were injected with AZ-NPs (40 mg / kg Ac4ManNAz, 200 μl) through the tail vein for four consecutive days, and the control group was injected with equal amounts of free Ac4ManNAz and PBS. Subsequently, the heart, liver, spleen, lung, kidney and tumor of each group of mice were taken, protein was extracted and quantified, and the bio-orthogonal level of each tissue was detected by Western blotting. At the same time, further detection was performed by fluorescent probe, that is, the tissue sections were blocked with 5% BSA for 2 hours and then labeled with DBCO-Cy5 (20 μM) for 30 minutes. After washing with PBS, DAPI was used to stain the cell nuclei respectively, and then imaged.

[0065] like Figure 5 As shown in the figure: All organs in the AZ-NPs group had strong bioorthogonal reactions, and the bioorthogonal reactions in tumors were significantly higher than those in the control group ( Figure 5 A-C), tissue immunofluorescence also further confirmed this conclusion ( Figure 5 D), and the rapid dynamic imaging of the tumor 30 minutes after the injection of DBCO-Cy5 also shows that the sensitivity of tumor imaging is high.

[0066] 7. Tumor bioimaging studies based on AZ-NPs

[0067] A20 tumor-bearing mice were injected with AZ-NPs (40 mg / kg Ac4ManNAz, 200 μl) through the tail vein for four consecutive days, and the control group was injected with equal amounts of free Ac4ManNAz and PBS. On the fifth day, DBCO-Cy5 (2.5 mg / kg) was injected through the tail vein for labeling for 30 minutes, and the signal at the tumor site was dynamically monitored by small animal in vivo imaging.

[0068] like Figure 6 As shown in: In vivo imaging data of small animals at multiple time points confirmed that the signal intensity of the local tumor in the AZ-NPs group was significantly higher than that in the free AZ group ( Figure 6 In addition, in vitro organ imaging of various organs also further demonstrated the high accumulation of DBCO-Cy5 in tumors ( Figure 6C), and it is worth noting that the signal intensity of the AZ-NPs+DBCO-Cy5 group in the mouse heart, liver, spleen, lung, and kidney is almost the same as that of the FreeAZ+DBCO-Cy5 group, but the signal intensity in the local tumor is significantly improved compared with FreeAZ+DBCO-Cy5, with high specificity ( Figure 6 Middle D), similarly, the rapid dynamic imaging of the tumor 30 minutes after the injection of DBCO-Cy5 also shows that the sensitivity of tumor imaging is high.

[0069] Based on bio-orthogonal click chemistry reaction, a new strategy for tumor-specific imaging using azidosugar nanoparticles is proposed. After injection, azidosugar nanoparticles accumulate in large quantities in the tumor site through the EPR effect (Enhanced Permeability and Retention) and are taken up by tumor cells. After a series of sugar metabolism biological pathways, the azido group is displayed on the surface of tumor cells to form an "artificial ligand". This process greatly improves the specificity of the imaging agent for tumor tissue and significantly reduces the background noise problem caused by nonspecific accumulation. Subsequently, the "artificial ligand" DBCO (Dibenzocyclooctyne) modified with the azide group is injected to achieve specific imaging of tumor tissue through click chemistry reaction. This reaction is fast and efficient under physiological conditions and has a high degree of chemical selectivity, thereby significantly improving the imaging signal intensity of tumor tissue and achieving a high-sensitivity tumor imaging effect.

[0070] It will be clear to those skilled in the art that various modifications to the above embodiments may be made without departing from the overall spirit and concept of the present invention. All of these modifications fall within the scope of protection of the present invention. The protection scheme of the present invention shall be subject to the claims attached to the present invention.

Claims

1. Application of tetraacetyl-2-amino-2-deoxy-2-azido-mannose in the preparation of tumor-specific imaging agents; wherein, The tetraacetyl-2-amino-2-deoxy-2-azido-mannose is used for enhancing the sensitivity and specificity of the tumor-specific imaging agent to tumor imaging.

2. Application of polyethylene glycol-block-polylactic acid combined with tetraacetyl-2-amino-2-deoxy-2-azido-mannose in the preparation of tumor-specific imaging agents; wherein, The polyethylene glycol-block-polylactic acid is PEG5k-b-PLA8k.

3. A method for preparing azidosugar nanoparticles, characterized in that: The steps include: S1, dissolving polyethylene glycol-block-polylactic acid and tetraacetyl-2-amino-2-deoxy-2-azido-mannose in dimethyl sulfoxide, and slowly adding the resulting solution into ultrapure water; S2. The dialyzed fluid is collected and freeze-dried to obtain azidosugar nanoparticles.

4. The method for preparing azidosugar nanoparticles according to claim 3, characterized in that: In step S1, polyethylene glycol-block-polylactic acid and tetraacetyl-2-amino-2-deoxy-2-azido-mannose are added to dimethyl sulfoxide in a ratio of 4:1 to 10:1 and stirred thoroughly; the concentration of dimethyl sulfoxide is 10±0.5 mg / mL.

5. The method for preparing azidosugar nanoparticles according to claim 3, characterized in that: In step S1, the solution formed by dissolving polyethylene glycol-block-polylactic acid and tetraacetyl-2-amino-2-deoxy-2-azido-mannose in dimethyl sulfoxide is added dropwise into ultrapure water; and / or, in step S1, the molecular weight of polyethylene glycol in the polyethylene glycol-block-polylactic acid is 5k, and the molecular weight of polylactic acid is 8k, and in step S2, dialysis is performed using a dialysis bag of 2000 to 14000 Da and ultrapure water.

6. Azidosugar nanoparticles prepared by the method for preparing azidosugar nanoparticles according to any one of claims 3 to 5.

7. Use of the azidosugar nanoparticles according to claim 6 in the preparation of a solid tumor specific imaging agent.

8. The use according to claim 7; wherein: The tumor-specific imaging agent is a lymphoma-specific imaging agent; the tumor-specific imaging agent is an injection preparation.

9. The use according to claim 7; wherein: The effective concentration of azidosugar nanoparticles is 5 to 100 μg / ml; the tumor-specific imaging agent also includes fluorescein or radionuclide probe modified by dibenzocyclooctyne; the fluorescein or radionuclide probe modified by dibenzocyclooctyne and the azidosugar nanoparticles form a combination agent, the azidosugar nanoparticles are the first injection agent, and the fluorescein or radionuclide probe modified by dibenzocyclooctyne is the second injection agent.

10. A lymphoma-specific imaging agent, characterized in that: The invention comprises the azidosugar nanoparticles and the fluorescein or radionuclide probe modified by dibenzocyclooctyne as claimed in claim 6; and the azidosugar nanoparticles and the fluorescein or radionuclide probe modified by dibenzocyclooctyne form a combined agent, the azidosugar nanoparticles are the first injection, and the fluorescein or radionuclide probe modified by dibenzocyclooctyne is the second injection.

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