Active oxygen responsive release and in-vivo imaging nano-drug carrier as well as preparation method and application thereof
The nanodrug carrier combined with mesoporous nanosilicon dioxide and citric acid-metformin-rhodamine carbon quantum dots solves the side effects of traditional drugs in the treatment of osteoporosis, realizes the controlled drug sustained release and in vivo imaging functions in high reactive oxygen environments, and improves the safety and effectiveness of the treatment.
Patent Information
- Application Number
- CN202510378582.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-03-28
- Publication Date
- 2025-06-27
AI Technical Summary
Traditional medicines treat osteoporosis with a range of side effects, including inhibiting bone turnover and increasing the risk of serious complications, such as atypical fractures and jaw osteonecrosis.
A nanodrug carrier of reactive oxygen response release and in vivo imaging of biological nanodrugs was prepared by combining mesoporous nanosilica, ketothyol carboxyl groups and citric acid-metformin-rhodamine carbon quantum dots. This carrier can sustainably release sodium aron phosphate in a high reactive oxygen environment and also has fluorescence imaging function.
The effect of controlled sustained-release drugs in the high reactive oxygen environment in the body of osteoporosis patients is achieved, and the function of in vivo imaging is also achieved, which reduces the side effects of the drugs and improves the safety and effectiveness of the treatment.
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Figure CN120204429A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of drug carriers, and particularly to a preparation method of a reactive oxygen species-responsive release and in-vivo imaging nanodrug carrier. The reactive oxygen species-responsive release and in-vivo imaging nanodrug carrier prepared by this preparation method, and the application of the drug carrier as a drug carrier for treating osteoporosis. Background Art
[0002] Osteoporosis (OP) is a systemic bone disease caused by various reasons, mainly characterized by decreased bone density and bone mass, damaged bone microstructure, increased bone fragility, and a state prone to fractures, which is common in the elderly and postmenopausal women.
[0003] When the normal bone remodeling process is disturbed by aging, estrogen deficiency or lack of exercise, the increased activity of osteoclasts leads to more bone mass loss or the weakened function of osteoblasts results in less bone mass formation, leading to insufficient bone formation to compensate for the increased bone resorption, and thus the onset of osteoporosis. Based on the mechanism of bone homeostasis and the pathological mechanism of osteoporosis, the drug design for osteoporosis mainly focuses on maintaining the balance between bone resorption and bone formation. Therapeutic agents are divided into three categories: antiresorptive agents, anabolic agents, and selective estrogen receptor modulators (SERMs). They inhibit osteoclastogenesis or promote osteogenesis to maintain bone homeostasis. However, long-term use of drugs will inhibit bone turnover, thus damaging natural bone repair. Therefore, these drugs will increase the risk of serious complications, such as atypical fractures and osteonecrosis of the jaw (ONJ).
[0004] In view of the series of side effects of traditional drug treatment methods, alternative strategies based on experimental biomaterials are promising to combat osteoporosis. Due to their precise targeting ability, lower doses are required. This helps to alleviate or even eliminate the side effects caused by drugs. Mesoporous silica nanoparticles (mSiO2, MSNs) have good biocompatibility, an inherent and stable silica skeleton, excellent mechanical strength, a large specific surface area, and the mesoporous channels endow them with the ability to store and release drug molecules and high thermal stability. More importantly, the surface of MSNs has a large number of hydrophilic silanol groups, making it easy to functionalize, and it can also act as a protective layer in vivo to prevent enzyme / pH-mediated drug degradation.
[0005] Carbon dots (CDs) are a new type of carbon-based zero-dimensional nanomaterials with excellent photoluminescence properties, modifiability, and biocompatibility. In addition, the preparation process of carbon dots is relatively simple, so they have a wide range of applications in the biomedical field. Carbon dot fluorescence imaging is a non-invasive, highly sensitive, and high-resolution bioimaging technology that can be used for cell imaging and play a role in diagnosis and adjuvant therapy. In this context, a nanodrug carrier with the advantages of MSNs and CDs, which has the functions of reactive oxygen species-responsive release and in vivo imaging, was designed and synthesized. Summary of the Invention
[0006] In view of this, to solve a series of side effects of traditional drug treatment for osteoporosis in the prior art, on the one hand, the present invention provides a preparation method of a nanodrug carrier with reactive oxygen species-responsive release and in vivo imaging. Based on mesoporous nano-silica, ketothiol carboxyl, and citric acid-metformin-rhodamine carbon quantum dots, a nanodrug carrier with reactive oxygen species-responsive release of alendronate sodium and fluorescence imaging is obtained, which has the advantages of simple preparation and convenient operation.
[0007] To achieve the above object, the present invention provides the following technical solutions:
[0008] A preparation method of a nanodrug carrier with reactive oxygen species-responsive release and in vivo imaging includes the following steps:
[0009] Step (1): Amination modification is carried out on mesoporous nano-silica particles to obtain amination-modified mesoporous nano-silica;
[0010] Step (2): Propane-2,2-diylbis(thio)diacetic acid is reacted with amination-modified mesoporous nano-silica to obtain ketothiol-grafted mesoporous nano-silica;
[0011] Step (3): Alendronate sodium is mixed with ketothiol-grafted mesoporous nano-silica to obtain ketothiol-grafted mesoporous nano-silica loaded with alendronate sodium;
[0012] Step (4): Citric acid-metformin-rhodamine carbon quantum dots are synthesized using citric acid, metformin hydrochloride, and rhodamine R6G as raw materials;
[0013] Step (5): Amination modification is carried out on citric acid-metformin-rhodamine carbon quantum dots to obtain amination-modified citric acid-metformin-rhodamine carbon quantum dots;
[0014] Step (6): The ketothiol-grafted mesoporous nano-silica loaded with alendronate sodium is reacted with amination-modified citric acid-metformin-rhodamine carbon quantum dots to obtain a nanodrug carrier with the functions of reactive oxygen species-responsive release and in vivo imaging.
[0015] Preferably, in step (1), mesoporous nano-silica particles are prepared by using the hydrolysis reaction of tetraethyl orthosilicate and water.
[0016] Preferably, in step (1), the mesoporous nano-silica particles are aminated with γ-aminopropyltriethoxysilane. Among them, the concentration of the mesoporous nano-silica particles is 3.33 mg / mL, and the concentration of γ-aminopropyltriethoxysilane is 0.67%.
[0017] Preferably, in step (2), the concentration of propane-2,2-diylbis(sulfanyl)diacetic acid is 3.2 mg / mL, and the concentration of the aminated mesoporous nano-silica is 10 mg / mL.
[0018] Preferably, in step (3), the concentration of sodium alendronate is 5 mg / mL, and the concentration of the ketosulfide-grafted mesoporous nano-silica is 10 mg / mL.
[0019] Preferably, in step (4), the concentrations of citric acid, metformin hydrochloride, and rhodamine R6G are 200 mg / mL, 200 mg / mL, and 0.4 mg / mL, respectively.
[0020] Preferably, in step (5), the concentration of ethylenediamine is 200 mg / mL, and the concentration of the citric acid-metformin-rhodamine carbon quantum dots is 0.86%.
[0021] Preferably, in step (6), the concentration of the ketosulfide-grafted mesoporous nano-silica loaded with sodium alendronate is 10 mg / mL, and the concentration of the aminated citric acid-metformin-rhodamine carbon quantum dots is 0.8 mg / mL.
[0022] In the second aspect, the present invention also provides a nano-drug carrier for reactive oxygen species-responsive release and in vivo imaging, which is prepared by the above preparation method.
[0023] In the third aspect, the present invention also provides the application of the above nano-drug carrier for reactive oxygen species-responsive release and in vivo imaging as a drug carrier for the treatment of osteoporosis.
[0024] The present invention has the following beneficial effects compared with the prior art:
[0025] The present invention relates to a method for preparing a nano-drug carrier for reactive oxygen species (ROS)-responsive release and in vivo imaging. This method is based on the combination of mesoporous nano-silica, ketothiol carboxyl group, and citric acid-metformin-rhodamine carbon quantum dots to prepare a nano-drug carrier that can respond to ROS and release alendronate sodium, while also having the function of fluorescence imaging. The advantages of this method are that the preparation process is simple, the raw materials required are easy to obtain, the yield is high, the cost is low, the operation is convenient, the purification process is simple, and the yield is relatively high.
[0026] The nano-drug carrier for ROS-responsive release and in vivo imaging obtained by the preparation method of the present invention utilizes the mesoporous structure on the surface of mesoporous nano-silica to achieve the loading and release of the anti-osteoporosis drug alendronate sodium. The carbon quantum dots are encapsulated and controlled released by grafting with ROS-sensitive ketothiol bonds. In addition, the carbon quantum dots can generate fluorescence when excited, thus endowing the nano-drug carrier with the function of fluorescence imaging. This nano-drug carrier can respond to and slowly release drugs in the high-ROS environment in the body of osteoporosis patients, while performing fluorescence imaging, so it has very broad application prospects in the treatment of osteoporosis and the prevention of related complications.
[0027] In the nano-drug carrier for ROS-responsive release and in vivo imaging prepared by the present invention, mesoporous nano-silica (MSN) and carbon quantum dots are connected by ketothiol bonds. In the high-ROS microenvironment of osteoporotic bone tissue, these ketothiol bonds will break, causing the carbon quantum dots to separate from the surface of MSN, exposing the mesoporous channels of MSN. At this time, the alendronate sodium molecules in the channels begin to be slowly released, thus achieving controlled and slow release of drugs to osteoporotic bone tissue.
[0028] The nano-drug carrier for ROS-responsive release and in vivo imaging prepared by the present invention has good adaptability. By changing the reaction conditions, the types of loaded drugs, and the types of chemical bonds for responsive release, it can be adapted to more different usage environments. Therefore, this nano-drug carrier has very broad application prospects. Description of the Drawings
[0029] Figure 1 The TEM image of the mesoporous nano-silica prepared in Example 1 is shown.
[0030] Figure 2 The TEM image of the metformin carbon quantum dots prepared in Example 1 is shown.
[0031] Figure 3 The TEM image of the drug carrier prepared in Example 1 is shown.
[0032] Figure 4 The Fourier transform infrared spectrum of the drug carrier prepared in Example 1 is shown.
[0033] Figure 5 The figure showing the CCK-8 experimental results of the drug carrier prepared in Example 1.
[0034] Figure 6 The figure showing the cell viability and cytotoxicity assay results of the drug carrier prepared in Example 1.
[0035] Figure 7 The figure showing the drug release test results of the drug carrier prepared in Example 1.
[0036] Figure 8 The figure showing the drug release test results of the prepared drug-loaded unmodified MSNs. Detailed implementation mode
[0037] The present invention provides a preparation method of a reactive oxygen species-responsive release and in vivo imaging nano drug carrier, comprising the following steps:
[0038] Step (1): Amination modification of mesoporous nano-silica particles to obtain aminated modified mesoporous nano-silica. Among them, mesoporous nano-silica particles are prepared by the hydrolysis reaction of tetraethyl orthosilicate and water. The hydrolysis reaction occurs at the interface of the aqueous phase and the organic phase, where the aqueous phase composition is ultrapure water, dodecyltrimethylammonium chloride and triethanolamine, the concentration of dodecyltrimethylammonium chloride is 25%, and the concentration of triethanolamine is 0.75%; the organic phase composition is decahydronaphthalene and tetraethyl orthosilicate, and the volume ratio of the two is 3:1, and the volume ratio of the aqueous phase to the organic phase is 2.5:1; the hydrolysis reaction condition is hydrothermal reaction at 60 °C for 12 hours. In this step (1), γ-aminopropyltriethoxysilane is preferably used for the amination modification of mesoporous nano-silica particles. In the amination modification reaction of mesoporous nano-silica particles, the reaction solvent is preferably toluene; the concentrations of mesoporous nano-silica particles and γ-aminopropyltriethoxysilane are 3.33 mg / mL and 0.67% respectively; the reaction condition is oil bath heating reflux reaction at 90 °C for 36 hours.
[0039] Step (2): React propane-2,2-diylbis(thio)diacetic acid with aminated modified mesoporous nano-silica to obtain ketone thiol grafted mesoporous nano-silica. In this step (2), in the ketone thiol grafting reaction, the solvent is dimethyl sulfoxide; the concentrations of propane-2,2-diylbis(thio)diacetic acid and aminated modified mesoporous nano-silica are 3.2 mg / mL and 10 mg / mL respectively; at the same time, N-hydroxysuccinimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide need to be added to the reaction system, and the concentrations are 2.24 mg / mL and 3.6 mg / mL respectively; the reaction condition is reaction at room temperature for 24 hours.
[0040] Step (3): Mix sodium alendronate with ketothiol-grafted mesoporous nanosilica to obtain ketothiol-grafted mesoporous nanosilica loaded with sodium alendronate. In this step (3), the solvent is ultrapure water, and the concentrations of sodium alendronate and ketothiol-grafted mesoporous nanosilica are 5 mg / mL and 10 mg / mL respectively; the reaction conditions are stirring at room temperature for 6 hours.
[0041] Step (4): Synthesize citric acid-metformin-rhodamine carbon quantum dots using citric acid, metformin hydrochloride, and rhodamine R6G as raw materials. In this step (4), in the preparation reaction of carbon quantum dots, the solvent is ultrapure water; the concentrations of citric acid, metformin hydrochloride, and rhodamine R6G are 200 mg / mL, 200 mg / mL, and 0.4 mg / mL respectively; the reaction conditions are reacting at 180 °C for 7 hours in a high-pressure hydrothermal reaction kettle.
[0042] Step (5): Perform amination modification on citric acid-metformin-rhodamine carbon quantum dots to obtain aminated modified citric acid-metformin-rhodamine carbon quantum dots. In this step (5), in the amination modification reaction of carbon quantum dots, the solvent is ultrapure water; the concentrations of ethylenediamine and citric acid-metformin-rhodamine carbon quantum dots are 200 mg / mL and 0.86% respectively; at the same time, N-hydroxysuccinimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide need to be added to the reaction system, with concentrations of 15 mg / mL and 25 mg / mL respectively; the reaction conditions are reacting at room temperature for 24 hours.
[0043] Step (6): React ketothiol-grafted mesoporous nanosilica loaded with sodium alendronate with aminated modified citric acid-metformin-rhodamine carbon quantum dots to obtain a nanodrug carrier with reactive oxygen-responsive release and in-vivo imaging functions. In this step (6), in the composite carrier preparation reaction, the solvent is dimethyl sulfoxide; the concentrations of ketothiol-grafted mesoporous nanosilica loaded with sodium alendronate and aminated modified citric acid-metformin-rhodamine carbon quantum dots are 10 mg / mL and 0.8 mg / mL respectively; at the same time, N-hydroxysuccinimide and 1-ethyl-(3-dimethylaminopropyl)carbodiimide need to be added to the reaction system, with concentrations of 2.24 mg / mL and 3.6 mg / mL respectively; the reaction conditions are reacting at room temperature for 24 hours.
[0044] In a second aspect, the present invention also provides a reactive oxygen species-responsive release and in-vivo imaging nanomedicine carrier, which is prepared by the above preparation method. This reactive oxygen species-responsive release and in-vivo imaging nanomedicine carrier utilizes the mesoporous structure on the surface of mesoporous silica nanoparticles to achieve the loading and release of alendronate sodium, an anti-osteoporosis drug. Carbon quantum dots are encapsulated and released in a controlled manner by grafting with thioacetal bonds sensitive to reactive oxygen species. Mesoporous silica nanoparticles (MSNs) and carbon quantum dots are connected by thioacetal ketone bonds. In the high reactive oxygen species microenvironment of osteoporotic bone tissue, these thioacetal ketone bonds will break, causing the carbon quantum dots to separate from the surface of MSNs, exposing the mesoporous channels of MSNs. At this time, the alendronate sodium molecules in the channels begin to be slowly released, thereby achieving controlled and slow release of drugs to osteoporotic bone tissue.
[0045] In addition, carbon quantum dots can produce fluorescence when excited, thus endowing the nanomedicine carrier with the function of fluorescence imaging. This nanomedicine carrier can respond to and slowly release drugs in the high reactive oxygen species environment in the body of osteoporosis patients, while performing fluorescence imaging, so it has very broad application prospects in the treatment of osteoporosis and the prevention of related complications.
[0046] In a third aspect, the present invention also provides the application of the above reactive oxygen species-responsive release and in-vivo imaging nanomedicine carrier as a drug carrier for treating osteoporosis.
[0047] The following combines specific embodiments to clearly and detailedly describe the technical solutions of the present invention.
[0048] Example 1
[0049] Preparation of a nanomedicine carrier capable of reactive oxygen species-responsive release and in-vivo imaging
[0050] Weigh 7.5 g of dodecyltrimethylammonium chloride and 22.5 g of ultrapure water in a clean beaker, then add 0.225 g of triethanolamine, and heat it in a water bath at 65 °C for 1 h until it is completely dissolved. Weigh another 8 mL of TEOS and 24 mL of decahydronaphthalene in a centrifuge tube, and mix them thoroughly by ultrasound. Subsequently, transfer the prepared TEA-CTAC-H2O solution to a round-bottom flask and stir magnetically, add 48 mL of ultrapure water, stop stirring after mixing evenly, and slowly pour 32 mL of the TEOS decahydronaphthalene solution along the wall of the cup into the flask. After obvious two-phase stratification appears, heat it in a water bath at 65 °C and stir magnetically for 12 h. After the reaction is completed, wait for the reaction solution to cool to room temperature, separate the aqueous phase with a separatory funnel, centrifuge at 10000 rmp for 5 minutes to obtain a white precipitate, wash it twice with absolute ethanol and ultrapure water respectively, dry and grind it, and then calcine it in a muffle furnace at 550 °C for 6 hours to obtain mesoporous silica nanoparticles (MSNs).
[0051] Take 200 mg of MSNs in a round-bottom flask, add 60 mL of toluene, ultrasonically disperse it evenly, then add 400 μL of γ-aminopropyltriethoxysilane, and reflux the reaction in an oil bath at 90 °C for 36 hours. After the reaction is completed, wait for the reaction solution to cool to room temperature, centrifuge at 10000 rmp for 5 minutes, take the white precipitate, wash it once with absolute ethanol and ultrapure water respectively, and then freeze-dry to obtain amino-functionalized mesoporous silica nanoparticles (MSN-NH2).
[0052] Take 32 mg of propane-2,2-diylbis(thio)diacetic acid in a round-bottom flask, add 10 mL of dimethyl sulfoxide, 22.4 mg of N-hydroxysuccinimide and 36 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide, stir magnetically for activation for 10 minutes, then add 100 mg of MSN-NH2, ultrasonically disperse it, and stir magnetically at room temperature for 24 hours. After the reaction is completed, wash the product 3 times with ultrapure water and freeze-dry to obtain ketothiol-grafted mesoporous silica nanoparticles (MSN-TK).
[0053] Take the prepared MSN-TK in a centrifuge tube, add 10 mL of 5 mg / mL sodium alendronate aqueous solution, place it in a shaker and shake for 6 hours to complete the drug molecule loading, and obtain ketothiol-grafted mesoporous silica nanoparticles loaded with sodium alendronate (MSN-TK-ALN).
[0054] Take 1 g of citric acid, 1 g of metformin hydrochloride and 20 mg of rhodamine R6G in a beaker, add 25 mL of ultrapure water, stir magnetically to dissolve it completely, then place it in a reaction kettle made of polyphenylene (PPL), raise the temperature to 180 °C and react under high temperature and high pressure for 7 hours. After the reaction is completed, take out the cooled reaction solution, filter it through a 0.22 μm filter membrane, put it into a dialysis bag with a molecular weight cut-off of 300, and dialyze it with ultrapure water for 48 hours, and then freeze-dry to obtain metformin carbon quantum dots. Take 8.4 mg of the carbon quantum dots in a round-bottom flask, add 12 mL of ultrapure water, 180 mg of N-hydroxysuccinimide and 300 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide, mix evenly, stir magnetically for activation for 10 minutes, add 104 μL of ethylenediamine, and react at room temperature for 24 hours. After the reaction is completed, use a dialysis bag with a molecular weight cut-off of 300 to dialyze the reaction solution with ultrapure water for 24 hours, and then freeze-dry to obtain amino-modified metformin carbon quantum dots.
[0055] Take the prepared MSN-TK-ALN in a round-bottom flask, add 10 mL of dimethyl sulfoxide, 22.4 mg of N-hydroxysuccinimide and 36 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and magnetically stir for activation for 10 minutes. Then add amino-modified metformin carbon quantum dots, ultrasonically disperse and magnetically stir at room temperature for 24 hours. After the reaction, wash the product 3 times with ultrapure water and freeze-dry to obtain a nano-drug carrier (MSN-TK-CD) with the functions of reactive oxygen-responsive release and in vivo imaging.
[0056] As Figure 1 shown in the transmission electron microscopy image of the MSNs obtained in Example 1, it shows that they have a relatively uniform particle size and good dispersibility, and the average particle size is 36 nm. As Figure 2 shown in the transmission electron microscopy image of the carbon dots obtained in Example 1, it shows that they have a small size and good dispersibility, and the average particle size is 4 nm. As Figure 3 shown in the transmission electron microscopy image of the composite carrier obtained in Example 1, it shows that its morphology is the form of cross-linked carbon quantum dots encapsulating MSN particles. As Figure 4 shown in the Fourier transform infrared spectroscopy image of the composite carrier obtained in Example 1, it shows that it has rich functional groups.
[0057] Next, the reactive oxygen-responsive release and in vivo imaging nano-drug carrier prepared in Example 1 was verified as follows:
[0058] Perform cell viability and dead cell detection and co-culture with the composite carrier
[0059] Take P3 bone marrow mesenchymal stem cells, seed them into a 24-well plate, about 6×103 cells per well, and incubate in a 37°C, 5% CO2 incubator for 24 hours. Then aspirate the culture medium, add 1 mL of PBS to each well to wash the cells; discard the PBS solution, add 1 mL of culture medium containing composite carriers with different concentrations to each well, and incubate for 24 hours. Under dark conditions, discard the culture medium, wash 3 times with PBS, add calcein / ethidium iodide (Calcein-AM / PI) and co-culture with the cells in a 37°C, 5% incubator for 30 min; then observe the cell survival images with a laser confocal microscope.
[0060] As Figure 6 shown in the experimental results, the cells have no obvious toxic reaction in the drug carrier environment with a concentration of 50 μg / mL and below.
[0061] Perform the drug-responsive release test of the composite carrier
[0062] Take 40 mg of the drug-loaded composite carrier, place it in a dialysis bag with a molecular weight cut-off of 3500 kDa, and disperse it in 20 mL of PBS containing hydrogen peroxide at different concentrations. At different time points, take 10 mL of the sample solution, and then add 10 mL of PBS solution to make up the volume. Let the sample solution taken each time stand for 2 h, then take 1 mL of each and add it to a centrifuge tube. Then add 0.5 mL of 0.05 mol / L sodium bicarbonate solution and 0.3 mL of 2% ninhydrin ethanol solution. After mixing evenly, react in a water bath at 90 °C for 20 min until the color is stable. Take it out and cool it, add an equal volume of 50% ethanol, mix evenly, and measure the absorption intensity at 568 nm with a UV-visible spectrometer to characterize the concentration of alendronate sodium. This test is carried out in 3 groups, and the results are averaged.
[0063] As Figure 7 shown in the results, the drug carrier has an oxidation environment-responsive release function.
[0064] Comparative Example 1
[0065] Perform the release test of the unmodified drug carrier
[0066] Use MSNs particles to obtain unmodified MSNs loaded with alendronate sodium according to the method in Example 1, and measure the drug release performance of the drug-loaded unmodified MSNs in PBS according to the steps of the above-mentioned composite carrier drug-responsive release test.
[0067] As Figure 8 shown in the results, MSNs immediately release alendronate sodium in PBS and do not have the responsive release performance.
[0068] The above; only the preferred specific embodiments of the present invention; but the protection scope of the present invention is not limited thereto; any person skilled in the art within the technical scope disclosed by the present invention; according to the technical solution of the present invention and its improved concept, make equivalent substitutions or changes; should be covered by the protection scope of the present invention.
Claims
1. A method for preparing a nano drug carrier for active oxygen responsive release and in vivo imaging, characterized in that: The steps include: Step (1), aminated mesoporous nano-silica particles to obtain aminated mesoporous nano-silica; Step (2), reacting propane-2,2-diylbis(sulfur)diacetic acid with amino-modified mesoporous nano-silica to obtain thioketal-grafted mesoporous nano-silica; Step (3), mixing sodium alendronate with thioketal-grafted mesoporous nano-silica to obtain thioketal-grafted mesoporous nano-silica loaded with sodium alendronate; Step (4), using citric acid, metformin hydrochloride and rhodamine R6G as raw materials to synthesize citric acid-metformin-rhodamine carbon quantum dots; Step (5), performing amino modification on the citric acid-metformin-rhodamine carbon quantum dots to obtain amino-modified citric acid-metformin-rhodamine carbon quantum dots; Step (6), reacting the thioketal-grafted mesoporous nano-silica loaded with sodium alendronate with amino-modified citric acid-metformin-rhodamine carbon quantum dots to obtain a nano-drug carrier with active oxygen response release and in vivo imaging functions.
2. The method for preparing a nano drug carrier for active oxygen responsive release and in vivo imaging according to claim 1, characterized in that: In step (1), mesoporous nano-silica particles are prepared by hydrolyzing ethyl orthosilicate with water.
3. The method for preparing a nano drug carrier for active oxygen responsive release and in vivo imaging according to claim 1, characterized in that: In step (1), γ-aminopropyltriethoxysilane is used to perform amino modification on the mesoporous nano-silica particles, wherein the concentration of the mesoporous nano-silica particles is 3.33 mg / mL, and the concentration of γ-aminopropyltriethoxysilane is 0.67%.
4. The method for preparing a nano drug carrier for active oxygen responsive release and in vivo imaging according to claim 1, characterized in that: In step (2), the concentration of propane-2,2-diylbis(thio)diacetic acid is 3.2 mg / mL, and the concentration of amino-modified mesoporous nano-silica is 10 mg / mL.
5. The method for preparing a nano drug carrier for active oxygen responsive release and in vivo imaging according to claim 1, characterized in that: In step (3), the concentration of sodium alendronate is 5 mg / mL, and the concentration of thioketal-grafted mesoporous nano-silica is 10 mg / mL.
6. The method for preparing a nano drug carrier for active oxygen responsive release and in vivo imaging according to claim 1, characterized in that: In step (4), the concentrations of citric acid, metformin hydrochloride and rhodamine R6G are 200 mg / mL, 200 mg / mL and 0.4 mg / mL, respectively.
7. The method for preparing a nano drug carrier for active oxygen responsive release and in vivo imaging according to claim 1, characterized in that: In step (5), the concentration of ethylenediamine is 200 mg / mL, and the concentration of citric acid-metformin-rhodamine carbon quantum dots is 0.86%.
8. A method for preparing a nano drug carrier for active oxygen responsive release and in vivo imaging according to any one of claims 1 to 7, characterized in that: In step (6), the concentration of the thioketal-grafted mesoporous nano-silica loaded with sodium alendronate was 10 mg / mL, and the concentration of the amino-modified citric acid-metformin-rhodamine carbon quantum dots was 0.8 mg / mL.
9. A nano drug carrier for active oxygen responsive release and in vivo imaging, characterized in that: The method is prepared according to any one of claims 1 to 8.
10. Use of the active oxygen responsive release and in vivo imaging nano drug carrier of claim 9 as a drug carrier for treating osteoporosis.