CN112773896A - Preparation method and application of MOFs-based nano composite - Google Patents
Preparation method and application of MOFs-based nano composite Download PDFInfo
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Abstract
The invention relates to a preparation method of MOFs-based nano composite, which comprises the following steps: loading nano Au aqueous solution on a UiO-66 metal organic framework, adding ASO aqueous solution of CA IX with a certain concentration, reacting for 8-12 hours at 10-20 ℃ at 50-120rpm, and then adding PEG-SH, reacting for 8-12 hours at 10-20 ℃ at 50-120 rpm; and carrying out solid-liquid separation to obtain the MOFs-based nano composite. The nano-composite has the double targeting inhibition effect of a small molecular inhibitor and ASO on CA IX, and the radiosensitization effect given by the Au nano-material, can relieve hypoxia and enhance RT.
Description
Technical Field
The invention belongs to the technical field of metal organic materials and molecular biology, and relates to a preparation method and application of MOFs-based nano-composites.
Background
External beam based Radiotherapy (RT) using high energy ionizing radiation (e.g. X-rays, gamma rays, protons or electron beams) through the oxygen (O) in the tumor2) Generate Reactive Oxygen Species (ROS) to induce DNA damage to kill cancer cells, and have been widely used clinically to treat localized solid tumors at various stages. However, hypoxia, which results from the rapid proliferation of cancer cells and the consequent vascular deformation, severely reduces the sensitivity of tumors to conventional radiotherapy, in which case insufficient oxygen supply would prevent ionizing radiation-induced DNA damage and significantly impair the efficacy of radiotherapy. Therefore, how to overcome the resistance to radiotherapy caused by hypoxia has been an active topic of research. In view of this, it has been proposed and claimed to deliver O directly2Or in situ O triggered by external and/or intrinsic pathological stimuli2Cause tumor O2Elevation, as well as disruption of hypoxia-related signaling pathways by targeted protein inhibition or gene coding, is effective in reversing hypoxia-enhanced RT. Furthermore, to improve the response of a given radiation dose, nanomaterials with large X-ray attenuation coefficients can be used to promote the deposition of energy within the tumor to sensitize hypoxic cells to radiation.
One of the adaptive responses of tumor cells to hypoxia involves up-regulation and functional activation of carbonic anhydrase ix (ca ix). CA IX is a cell surface enzyme that catalyzes the formation of carbon dioxide and water into bicarbonate and protons (CO)2+H2O→HCO3 -+H+). Considering the extracellular-facing catalytic domain of CA IX, it contributes to the defectExtracellular acidification by oxygen, to produce HCO3 -Can be prepared by HCO3 -The transporter is transported back into the cytoplasm to buffer intracellular pH, thereby maintaining a neutral intracellular environment. Thus, CA IX is involved in the regulation of intracellular and extracellular pH perturbations caused by hypoxia-induced changes in cellular metabolism, producing excess acid, thereby promoting migration and invasion of tumor cells in hypoxic environments. Indeed, CA IX is recognized as a marker for poor survival and distant metastasis in aggressive cancers. Fortunately, CA IX is affected by tumor-specific overexpression, and expression in normal tissues is highly restricted, making it a potential and attractive therapeutic target for hypoxic tumors.
CA IX is a complex with zinc ion (Zn)2+) Core functional zinc metalloproteins, several Zn bearing proteins have been developed2+Small molecule inhibitors of the anchor group inhibit the enzymatic activity of CA IX, most of which belong to the sulfonamides and their bioisosteres (sulfamates, sulfenamides, etc.). For example, a BODIPY photosensitizer coupled to acetazolamide was designed to mitigate the effects of hypoxia based photodynamic therapy (PDT) and to exhibit enhanced PDT efficacy both in vitro and in vivo as compared to BODIPY. Another strategy relies on gene modulators of oligonucleotides, such as antisense oligonucleotides (ASOs) and small interfering rnas (sirnas), to silence CA IX protein expression by sequence-specifically knocking out targeted proteins without regard to complex protein structure. ASO are chemically modified single-stranded oligonucleotides 16-25 bases in length, intended to hybridize to messenger RNA (mRNA) levels in cells via Watson-Crick base pairing, thus providing unprecedented specificity. In the prior art, the co-inhibition of CA IX activity by molecular inhibitors and ASOs to enhance nanomaterial-mediated RT efficacy has not been studied, and how to organically assemble these important components together remains a challenge.
Disclosure of Invention
In view of the above, an object of the present invention is to provide a method for preparing a MOFs-based nanocomposite, and another object of the present invention is to provide a MOFs-based nanocomposite and applications thereof.
In order to achieve the purpose, the invention provides the following technical scheme:
the preparation method of the MOFs-based nano composite comprises the following steps:
loading nano Au aqueous solution on a UiO-66 metal organic framework, adding ASO aqueous solution of CA IX, reacting for 8-12 hours at 10-20 ℃ at 50-120rpm, and then adding PEG-SH, reacting for 8-12 hours at 10-20 ℃ at 50-120 rpm; and carrying out solid-liquid separation to obtain the MOFs-based nano composite.
Further, the final concentration of the ASO aqueous solution of CA IX was 2. mu.M.
Further, the ASO sequence of CA IX was ACACTGTGGCCATTGTTGCTT.
Further, the solid-liquid separation is centrifugal separation, and the centrifugal separation is carried out for 15-20min at 8000-10000 rpm.
Further, the preparation method of the aqueous solution of the UiO-66 metal organic framework loaded with the nano Au comprises the following steps:
dispersing UiO-66 in deionized water, fully stirring, dropwise adding chloroauric acid tetrahydrate solution, and stirring at normal temperature for 2-4 h; adding ice-cold 2mg/mL sodium borohydride aqueous solution, continuously stirring and reacting for 1-4 h, centrifuging and collecting the solid, washing for 2-4 times, and re-dispersing in deionized water for later use.
Further, in the preparation method of the aqueous solution of the UiO-66 metal organic framework loaded with the nano Au:
dispersing every 1mg of UiO-66 in 1mL of deionized water, and dropwise adding 50 mu L of 10mg/mL chloroauric acid tetrahydrate solution; add 40. mu.L of aqueous sodium borohydride solution.
Further, the preparation method of UiO-66 comprises the following steps:
respectively dissolving terephthalic acid and zirconium oxychloride octahydrate in DMF, mixing and stirring for more than 5min, and adding acetic acid; placing the mixture in an oil bath at the temperature of 110-130 ℃, and stirring and reacting for 5-6 h; and (3) centrifuging the obtained product, washing the product for 2-3 times by using DMF (dimethyl formamide) and deionized water respectively, and drying the product in vacuum.
Further, in the preparation method of UiO-66, the concentration of the DMF solution of terephthalic acid is 100mg/ml, the concentration of the DMF solution of zirconium oxychloride octahydrate is 7mg/ml, and the concentration of the DMF solution of terephthalic acid is as follows: DMF solution of zirconium oxychloride octahydrate: the volume ratio of acetic acid is 1:3: 2.
2. The MOFs-based nanocomposite obtained by any of the above methods of preparation.
The application of the MOFs-based nano-composite in the preparation of drugs or auxiliary reagents for the radiotherapy of hypoxic tumors.
Further, the hypoxic tumor is a human breast tumor.
The invention has the beneficial effects that: the invention provides a biodegradable nano composite material based on UiO-66MOF, which has double targeting inhibition effects of a small molecule inhibitor and ASO on CA IX, and radiosensitivity endowed by a high Z nano material, can relieve hypoxia and enhance RT, and the key point of the invention is that important components are organically assembled together. The present invention has been extensively tested to select terephthalic acid as the organic ligand to coordinate with the zirconium base to make UiO-66MOF and further serve as a platform to build hybrid composites by growing gold nanoparticles (Au NPs) in situ on the surface, followed by coupling with ASO via Au-S bonds. Enhancement of CA IX inhibition, Zn with CA IX2+Strongly bind to inhibit its enzymatic activity. The decoration of gold nanoparticles brings the following advantages: (i) as an effective radiosensitizer to facilitate radiation therapy; (ii) providing an active site for attachment of a thiolated ASO; (iii) promoting efficient pegylation to prevent the nanocomposite from aggregating in a physiological environment. Furthermore, the "all-in-one" nanocomposite material resides in an acidic tumor microenvironment, the biodegradable UiO-66 matrix will dissociate, and these previously integrated functional moieties will perform their respective functions and provide synergistic effects with each other. Thus, the designed nanocomposite can provide excellent anti-tumor efficacy as a drug or formulation in vivo and in vitro with substantial non-toxicity to the system, especially hypoxia-remitted enhanced RT for hypoxic triple negative (MBA-MD-231) breast cancer.
Drawings
In order to make the object, technical scheme and beneficial effect of the invention more clear, the invention provides the following drawings for explanation:
FIG. 1 shows the results of agarose gel electrophoresis of ASO at various concentrations of 0.5-4. mu.M and UAAP loaded with ASO.
FIG. 2 shows the survival ratio of MDA-MB-231 cells from different experimental groups after receiving different doses of radiation.
FIG. 3 is a flow chart showing the change in apoptosis in each experimental group.
FIG. 4 is a comparison of tumor growth curves of the experimental groups during the treatment process and the tumor volume after the treatment.
FIG. 5 is a TEM image of UiO-66/Au-ASO/PEG as a sample in example 1.
Detailed Description
Preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings. The experimental procedures, in which specific conditions are not specified in the examples, are generally carried out under conventional conditions or under conditions recommended by the manufacturers.
Example 1
1. Preparation of UiO-66 nano material
The method for preparing the UiO-66 nano particles by adopting a solvothermal method comprises the following specific steps:
(1) 200mg of terephthalic acid (BDC) was dissolved in 2mL of N, N-Dimethylformamide (DMF), and the solution was added to a round-bottomed flask and stirred for 5min or more.
(2) 42mg of zirconium oxychloride octahydrate (ZrOCl) was weighed2·8H2O) was dissolved in 6mL of DMF.
(3) 6mL of DMF in which zirconium oxychloride octahydrate was dissolved in (2) was added to (1), and after mixing and stirring the mixture for 5min, 4mL of acetic acid was added.
(4) The bottle cap of the round-bottom flask containing the mixed solution is covered, the round-bottom flask is placed in an oil bath at the temperature of 110 ℃, and the round-bottom flask is stirred to react for 5 hours.
(5) And (3) centrifuging the obtained product, washing the product for 2 times by using DMF (dimethyl formamide) and deionized water respectively, drying the product overnight in vacuum, collecting the UiO-66 nano material, weighing the nano material and calculating the yield.
UiO-66: CAS:1072413-89-8, metal organic frameworks, commercially available products, or prepared according to prior art methods.
2. Preparation of UiO-66/Au nano material
Au nano-particles are grown on the surface of UiO-66 in situ by adopting a reduction method, and the method comprises the following specific steps:
(1) 10mg of UiO-66 was weighed out and dispersed in 10mL of deionized water sufficientlyStirring, 500. mu.L of 10mg/mL chloroauric acid tetrahydrate (HAuCl) was added dropwise4·4H2O) solution, and stirring for 2 hours at normal temperature.
(2) A2 mg/mL aqueous solution of sodium borohydride was prepared, and the mixture was placed on ice and cooled in advance.
(3) 400 μ L of ice-cold (0-4 ℃) aqueous sodium borohydride solution is added, and the reaction is continued for 1h with stirring at a low temperature of 10-20 ℃.
(4) The product was collected by centrifugation, washed 3 times with water and redispersed in deionized water for use.
3. Preparation of UiO-66/Au-ASO/PEG (UAAP, the same shall apply hereinafter) nano material
Adding 5mL of UiO-66/Au aqueous solution prepared in the step 2 (1 mg/mL) into a 50mL round bottom glass bottle, adding an excessive concentration of ASO (antisense oligonucleotide with the sequence of ACACTGTGGCCATTGTTGCTT) aqueous solution of CA IX (Carbonic Anhydrase IX ) (the final concentration of ASO is 2 mu M), and shaking overnight at 90rpm in a shaking table at 16 ℃; adding 1-5ml of PEG-SH (sulfhydryl polyethylene glycol) for continuous shaking overnight in the next day, wherein the adding amount of the PEG-SH is 1-4 times of the mass of UiO-66/Au; on day 3, the reaction liquid was taken out, centrifuged at 12000rpm for 20min by using a centrifuge, the supernatant was collected, the resulting precipitate was washed 2 times with ultrapure water, and finally the obtained UiO-66/Au-ASO/PEG was redispersed in 5mL of ultrapure water and stored at 4 ℃ for further use.
Example 2
The preparation method of UAP (UiO-66/Au-PEG) comprises the following steps:
taking 5mL of the aqueous solution of UiO-66/Au 1mg/mL prepared in the step 2, adding the aqueous solution into a 50mL round bottom glass bottle, adding 1-5mL of PEG-SH (sulfhydryl polyethylene glycol) and shaking the mixture overnight in a shaking table at the temperature of 16 ℃ at 90rpm, wherein the adding amount of the PEG-SH is 1-4 times of the mass of the UiO-66/Au; on day 3, the reaction liquid was taken out, centrifuged at 12000rpm for 20min by using a centrifuge, the supernatant was collected, the resulting precipitate was washed 2 times with ultrapure water, and finally the obtained UiO-66/Au-ASO/PEG was redispersed in 5mL of ultrapure water and stored at 4 ℃ for further use.
Example 3
FIG. 1 shows the results of agarose gel electrophoresis of different concentrations of ASO and ASO-loaded UAAP at 0.5-4. mu.M, showing that different UAAP precipitates with visible CA IX ASO bands and the corresponding supernatants are free of bands. The results show that the UAAP has higher nucleic acid loading capacity and higher stability.
FIG. 5 is a Transmission Electron Microscope (TEM) image of UiO-66/Au-ASO/PEG of example 1 sample, as shown by the image, an octahedron with a diameter of about 180nm and well-dispersed UiO-66NP (nanoparticles) were successfully prepared. Direct reduction of gold (III) chloride hydrate (HAuCl) by using sodium borohydride as reducing agent in an ice bath4·4H2O), gold nanoparticles can be modified on the surface of UiO-66. As shown in the figure, Au NP with the diameter of about 5-20 nm is distributed on the outer surface of the UiO-66/Au NP. Subsequently, the CA IX inhibitor of ASO-SH (ASO) was anchored to the bare Au NP via an Au-S bond, and then the UiO-66/Au-ASO NP was further modified with PEG-SH to prevent the physiological aggregation environment of the NP. The presence of each element (Zr, Au, P and S) in UiO-66/Au-ASO/PEG confirms the successful preparation of the hybrid nanoparticles as shown by the Energy Dispersive Spectroscopy (EDS) elemental mapping. Moreover, the distribution regions of the Au and S elements overlap significantly, which further demonstrates the generation of Au-S bonds.
Example 4
Because the DNA damage caused by radiotherapy can not cause tumor cell death quickly, long-time proliferation accumulation is needed to calculate the influence of radiotherapy on the proliferation of tumor cells, the influence of single Radiotherapy (RT) and radiotherapy combined with UiO-66/Au-PEG (UAP + RT group) and UiO-66/Au-ASO/PEG (UAAP + RT group) on the proliferation of MDA-MB-231 cells under hypoxic conditions is evaluated by a plate cloning experiment. Collecting MDA-MB-231 tumor cells in logarithmic growth phase, performing trypsin digestion, counting, adding into 6-well plate, inoculating cells at a density of 1000 cells per well, shaking 6-well plate until cells are dispersed sufficiently, and returning 6-well plate to 1% oxygen concentration hypoxic cell incubator (37 deg.C, 5% CO)2) Cultured overnight in the medium. Observing the cell adherence condition by an inverted microscope for the next day, adding each group of nano materials after adherence is normal until the final concentration is 25 mug/mL, continuously putting back to a hypoxic cell culture box with 1% oxygen concentration for culture overnight, removing the old culture medium for the next day, washing for 1 time by sterile PBS stored at room temperature, and adding a fresh culture medium. Irradiating each group of 6-hole plates with 2-8 Gy different doses of X raysAfter the irradiation is finished, the 6-well plate is put back to a hypoxic cell culture box with the oxygen concentration of 1% for culture. Observing the cell culture condition every 2 days, changing the culture medium every 4 days, continuing culturing for 10-14 days until cell mass can be seen by naked eyes, and stopping culturing. The old culture solution was removed, washed with sterile PBS placed at room temperature for 2 times, the cells in the 6-well plate were fixed with anhydrous methanol for 10min, the methanol was carefully removed, then 0.5mL of 1% crystal violet staining solution was added to each well, the staining solution was carefully removed after staining for 10min, the cells were washed with pure water for 2-4 times, and the 6-well plate was air-dried for cell counting.
Fig. 2 shows the survival ratio of MDA-MB-231 cells from different experimental groups after receiving different doses of radiation therapy, and the cell survival curves (calculated by the formula y ═ 1- (1-exp (-k x)) ^ N) fitted with the multi-target click model as the regression model, and the three survival curves correspond to the RT group, the UAP + RT group, and the UAAP + RT group from top to bottom, respectively. Table 1 shows the relevant parameters for the radiosensitization study. From the survival curves of the cells and the radiosensitization parameters, the average lethal dose Do of the single Radiation Therapy (RT) to the MDA-MB-231 is 2.089, Do is 1.82 after UAP + RT treatment and Do is 1.57 after UAAP + RT treatment, so that the combined therapy can reduce the average lethal dose of the MDA-MB-231 cells, and the UAAP effect is stronger than that of the UAP. The dosage Dq of RT group is 2.09 to overcome the shoulder area of the curve, and 1.82 after UAP treatment, which is obviously smaller than that of RT group, and 1.57 of UAAP + RT treatment group, which shows that the sensitivity of MDA-MB-231 cells to radiotherapy is obviously improved by UAAP + RT treatment. The radiation sensitization ratio (SER) of UAP + RT and UAAP + RT is 1.11 and 1.25 respectively, and the radiation sensitization effect is better. The UAP and UAAP constructed by the invention can obviously improve the sensitivity of MDA-MB-231 cells to X-rays.
TABLE 1 radiosensitization study of MDA-MB-231 cells and related parameters
Example 5
To further investigate whether the radiosensitizing effect of UiO-66/Au-ASO/PEG on MDA-MB-231 cells was associated with apoptosis, we examined various groups for apoptotic changes.
(1) MDA-MB-231 cells in logarithmic growth phase cultured in a 1% oxygen incubator (37 ℃, 5% CO2) were taken, digested into single cells, plated in a 6-well plate at an appropriate density, and cultured in a 1% oxygen incubator.
(2) And (3) removing the old culture medium when the cells grow to the proper density on the next day, adding the nano materials with different concentrations diluted by different culture media, washing for 2 times by using cold PBS after taking 4 hours, adding a fresh DMEM culture medium, and placing each treatment group in the 6-hole plate back to the 1% oxygen incubator for continuous culture for 48 hours after receiving 4Gy of X-ray irradiation.
(3) Collecting old cell culture solution of each treatment group in a 6-well plate, washing with cold PBS for 2 times, collecting PBS washing solution, digesting cells with pancreatin for 1-2 min, stopping digestion with the old cell culture solution, resuspending the cells, adding the collected PBS washing solution, and centrifuging at 900rpm for 5min by using a refrigerated centrifuge.
(4) The cell pellet was collected, gently resuspended in 100. mu.L Binding Buffer on ice, 5. mu.L Annexin V FITC and 10. mu.L PI staining solution were added, and stained in the dark for 30 min.
(5) After the staining was completed, each group of cells was transferred to a flow tube and the apoptotic changes were immediately analyzed on a flow machine.
The apoptosis results are shown in FIG. 3, and the apoptosis ratio of the cells without any treatment is only 2.04%. The apoptosis ratio of the UiO-66/Au-ASO/PEG treated cells after 24h is 4.75%, and the cells have no statistical difference (p is 0.357) with the Control group, which indicates that the UiO-66/Au-ASO/PEG has no obvious influence on the apoptosis, and simultaneously indicates that the biocompatibility of the UiO-66/Au-ASO/PEG to MDA-MB-231 cells is good. And the apoptosis ratio of the breast cancer cells irradiated by 4Gy X-rays for 48 hours is 14.35 percent, which is 7.03 times of that of the Control group, and the cell apoptosis ratio has statistical significance difference (p is 0.01). The apoptosis rate of the UiO-66/Au-ASO/PEG group is 4.75%, when the UiO-66/Au-ASO/PEG is used for incubating cells and then the cells are irradiated by 4Gy X-rays, the apoptosis ratio reaches 28.12%, which is 5.92 times that of the UiO-66/Au-ASO/PEG group, and the statistical difference is significant (p is 0.012). Therefore, the single X-ray treatment can promote the apoptosis, the single UiO-66/Au-ASO/PEG treatment of the cells can not induce obvious apoptosis, but the UiO-66/Au-ASO/PEG combined X-ray treatment can obviously promote the apoptosis of tumor cells, which shows that the UiO-66/Au-ASO/PEG can enhance the sensitivity of MDA-MB-231 cells to radiation and can be further prepared into an auxiliary drug or reagent for RT treatment.
Example 6
After the MDA-MB-231 breast cancer subcutaneous tumor-bearing mice are successfully modeled, the mice are randomly divided into 6 groups of 6 mice. A is a Control group (Control), B is a simple radiotherapy group (RT), C is Uio-66/Au-PEG group (UAP), D is Uio-66/Au-PEG + radiotherapy group (UAP + RT), E is UiO-66/Au-ASO/PEG group (UAAP), F is UiO-66/Au-ASO/PEG + radiotherapy group (UAAP + RT).
The length (L) and length (W) of the tumor were measured with a vernier caliper, according to the formula V ═ 0.5 XLXW2Estimating the tumor volume when the subcutaneous tumor of each group of nude mice grows to 50-100mm in volume3The treatment experiment was started on the left and right. The concentrations of UiO66, Uio-66/Au-PEG and UiO66/Au-ASO/PEG were adjusted to 1mg/mL by saline, 200. mu.L of saline was injected into the tail vein of each nude mouse in the afternoon, and an equal volume of saline was injected into the control group. 4Gy of radiation was given the following day. The dose was administered again on day 7 after the first treatment and the radiation treatment was given the next day. The tumor growth of nude mice was observed every other day after the start of treatment, the tumor length and width were measured, and the body weight of the mice was weighed. To ensure animal welfare tumor volume does not exceed 2000mm3The experiment is terminated before, the tumor-bearing nude mice are euthanized, and the nude mouse organs and tumors of each treatment group are collected. FIG. 4 shows the tumor growth curves (A) of the experimental groups and the tumor volume (B) after the treatment, wherein the curves of A in FIG. 4 are respectively Control group, UAP group, UAAP group, RT group, UAP + RT group and UAAP + RT group from top to bottom, and it can be seen from the figure that the treatment groups have the treatment effect on the growth of the tumor of the MDA-MB-231 nude mouse compared with the Control group which is not treated. The inhibition rate of UAP alone on the tumor volume was 23.59%, the inhibition rate of UAAP alone on the tumor volume was 40.49%, and the inhibition rate of RT alone on the tumor volume was 56.19%. Radiotherapy alone was more significant than treatment with the UAP and UAAP groups. The inhibition rates of the tumor volumes of the UAP + RT treatment and the UAAP + RT group are 70.04% respectively and 80.09% respectively, and the combined treatment is carried outThe tumor suppression effect of the treatment is significantly greater than RT alone. The tumor-inhibiting effect of UAAP + RT was most pronounced with a tumor volume of (203.47. + -. 105.54) mm at the end of the experiment3. The results show that both UAP and UAAP can enhance the inhibition effect of radiotherapy on tumor growth, and the UAAP effect is stronger.
Finally, it is noted that the above-mentioned preferred embodiments illustrate rather than limit the invention, and that, although the invention has been described in detail with reference to the above-mentioned preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the scope of the invention as defined by the appended claims.
Claims (10)
- A method for preparing a MOFs-based nanocomposite, comprising:loading nano Au aqueous solution on a UiO-66 metal organic framework, adding ASO aqueous solution of CA IX, reacting for 8-12 hours at 10-20 ℃ at 50-120rpm, and then adding PEG-SH, reacting for 8-12 hours at 10-20 ℃ at 50-120 rpm; and carrying out solid-liquid separation to obtain the MOFs-based nano composite.
- 2. The method of claim 1, wherein the final concentration of the ASO solution of CA IX is 2 μ M.
- 3. The method of preparing MOFs-based nanocomposites according to claim 1, wherein the solid-liquid separation is centrifugal separation, which is performed at 8000-10000 rpm for 15-20 min.
- 4. The method for preparing MOFs-based nanocomposite according to claim 1, wherein the method for preparing the aqueous solution of UiO-66 metal organic framework loaded with nano Au comprises the following steps:dispersing UiO-66 in deionized water, fully stirring, dropwise adding chloroauric acid tetrahydrate solution, and stirring at normal temperature for 2-4 h; adding ice-cold 2mg/mL sodium borohydride aqueous solution, continuously stirring and reacting for 1-4 h, centrifuging and collecting the solid, washing for 2-4 times, and re-dispersing in deionized water for later use.
- 5. The method for preparing MOFs-based nanocomposites according to claim 4, wherein the method for preparing the aqueous solution of UiO-66 metal organic framework loaded with nano Au comprises:dispersing every 1mg of UiO-66 in 1mL of deionized water, and dropwise adding 50 mu L of 10mg/mL chloroauric acid tetrahydrate solution; add 40. mu.L of aqueous sodium borohydride solution.
- 6. The method for preparing the MOFs-based nanocomposite according to any one of claims 1 to 5, wherein the UiO-66 is prepared by:respectively dissolving terephthalic acid and zirconium oxychloride octahydrate in DMF, mixing and stirring for more than 5min, and adding acetic acid; placing the mixture in an oil bath at the temperature of 110-130 ℃, and stirring and reacting for 5-6 h; and (3) centrifuging the obtained product, washing the product for 2-3 times by using DMF (dimethyl formamide) and deionized water respectively, and drying the product in vacuum.
- 7. The method of claim 6, wherein the UiO-66 is prepared by mixing terephthalic acid with DMF, zirconium oxychloride octahydrate with DMF, terephthalic acid with DMF at a concentration of 100mg/ml, and a mixture of terephthalic acid with DMF: DMF solution of zirconium oxychloride octahydrate: the volume ratio of acetic acid is 1:3: 2.
- 8. The MOFs-based nanocomposites obtained by the process of any of claims 1-7.
- 9. Use of the MOFs-based nanocomplexes of claim 8 for the preparation of drugs or adjuvant agents for the radiotherapy of hypoxic tumors.
- 10. The use of claim 9, wherein the hypoxic tumor is a human breast tumor.
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