CN111467491A - Synthesis of platinum modified MOF2-Pt-FA as bidirectional enhanced photodynamic therapy medicine and application of platinum modified MOF2-Pt-FA in tumor therapy - Google Patents
Synthesis of platinum modified MOF2-Pt-FA as bidirectional enhanced photodynamic therapy medicine and application of platinum modified MOF2-Pt-FA in tumor therapy Download PDFInfo
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Abstract
The invention discloses a platinum modified metal organic material MOF2-Pt-FA as a bidirectional enhanced photodynamic therapy medicament, a preparation method and application thereof; the preparation method comprises the following steps: firstly, preparing a two-dimensional MOF nano-sheet taking CuII as an active center, then depositing platinum nano-particles on the MOF2 surface, and then modifying the poly-MOF 2-Pt surface(ethylene glycol) -folic acid to enhance targeting and compatibility, and obtain the nano-drug; after uptake by targeted cells, the CuII in MOF2 can reduce the concentration of GSH, thereby enhancing the light-triggered reactive oxygen species level produced by the MOF; in addition, the prepared medicament platinum nanoparticles have catalase-like activity and can convert intracellular H2O2Decomposition to O2Experiments show that the combination of GSH exhaustion and hypoxia relief can obviously improve PDT efficiency; the metal organic nano material disclosed by the invention can be used as a nano medicament for photodynamic therapy and has clinical potential for treating tumors.
Description
Technical Field
The invention belongs to the technical field of biomedicine, and particularly relates to application of a platinum-modified metal organic framework material MOF2-Pt-FA as a bidirectional enhanced photodynamic therapy medicament in tumor treatment.
Background
In recent years, photodynamic therapy (PDT) has become a promising treatment, relying primarily on highly toxic Reactive Oxygen Species (ROS) generated by Photosensitizers (PS) under light irradiation. PDT is of widespread interest due to its unique advantages, such as specific spatio-temporal selectivity, negligible invasiveness and low systemic toxicity. However, so far, there are still some troublesome problems: (1) most PS have poor tumor targeting and aggregation capability, low effective load, easy aggregation, photoinduced quenching and the like; (2) Glutathione (GSH) levels in cancer cells are much higher (100-fold) than in normal cells, and the over-expressed glutathione can be used as an antioxidant to scavenge ROS generated under irradiation of light; (3) hypoxia is considered a characteristic of solid tumors due to O of PDT2Dependence, severely reduced the therapeutic effect.
To solve the first problem described above, the Metal Organic Framework (MOF) integrating the photosensitizer into the periodic structure has a high PS loading ratio, singlet oxygen: (1O2) Easy diffusion, inherent biodegradability, controllable size, these advantages open up a new door for photodynamic therapy. Due to the second problem of PDT, great efforts have been made to develop materials for reducing GSH. For example, copper ion-based nanocomposites (Cu)2 +-g-C3N4，Cu2 +MOF, Cu-TCPP), manganese ion-based nanosystems (MnO)2，MnFe2O4@ MOF core-shell nanostructures, MnIII-sealed MOF nanostructures), iron-doped polydiaminopyridine nanoshuttles and preparation of polymers that can reduce GSH levels in cells to enhance PDT effects. To solve the problemThe intrinsic inhibition of tumor hypoxia by PDT has explored a number of approaches to ameliorate tumor hypoxia, including direct delivery of oxygen, in situ generation of oxygen (catalase, MnO)2Pt nanoparticles, CaO2Carbon nitride, carbon dots) and enhance blood flow. Although each of the problems of PDT has been solved to some extent, the fact that current strategies suffer from unsatisfactory therapeutic effects or complex material synthesis will greatly inhibit its clinical application.
Disclosure of Invention
The purpose of the invention is as follows: to an intelligent and simple therapeutic nano-platform that can overcome all major limitations present in PDT to obtain better therapeutic effects.
The method does not need a complex synthesis preparation process, the in-situ deposition efficiency of the platinum nanoparticles on the surface of the material is high, the loading rate is high, severe reaction conditions are not needed, and the reaction conditions are mild. In addition, the prepared nano-drug has the characteristics of better biocompatibility and low toxicity, and can target specific tumor cells to perform in-vivo tumor treatment.
The technical scheme is as follows: in order to solve the technical problems, the technical scheme adopted by the invention is as follows: based on the application of platinum modified metal organic framework material MOF2-Pt-FA as a bidirectional enhanced photodynamic therapy drug in tumor treatment, in order to achieve the aim, a simple strategy for dual enhancement of PDT treatment effect by simultaneously consuming intracellular GSH and continuously relieving tumor hypoxia microenvironment is designed. Firstly, divalent copper ions (CuII) are used as an active center, porphyrin (TCPP) is used as a ligand to synthesize two-dimensional MOF2, then Pt nanoparticles are deposited on the surface of the MOF2 in situ, and finally PEG-FA is modified to form the nano-drug. The MOF2-Pt-FA has excellent biocompatibility and targeting capability. The MOF structure can prevent light-induced quenching of the photosensitizer (TCPP) and produce more ROS under light irradiation. Importantly, CuII in MOF2 can specifically bind and absorb GSH, resulting in decreased intracellular GSH concentrations and increased ROS levels. In addition, MOF2-Pt-FA can continuously convert intracellular H by utilizing the catalase-like activity inherent in Pt NPs2O2Is deposited as O2To alleviate hypoxia in tumorsAnd (4) environment. In vitro and in vivo experiments prove that integration of glutathione depletion and hypoxia relief obviously enhances the curative effect of PDT, thereby providing another cancer treatment method for clinic.
The application of the platinum modified metal organic framework material MOF2-Pt-FA as a bidirectional enhanced photodynamic in preparing a medicament for treating tumors.
The nano-drug MOF2-Pt-FA takes porphyrin (TCPP) as a ligand and divalent copper ions (CuII) as an active center, platinum nano-particles are deposited on the surface of the material in situ, and finally the material is wrapped by high polymer PEG-FA, so that the anti-cancer drug for promoting photodynamic therapy can be obtained.
Wherein the MOF2-Pt-FA has a size of 80-200 nm.
Wherein the size of the platinum nanoparticles loaded on the MOF2-Pt-FA surface is 2-10 nm.
Wherein the MOF2-Pt-FA can have catalase-like activity and efficiently decompose hydrogen peroxide at a concentration of 50-200 μ M at a pH of 5-6.
Wherein the cell culture conditions comprise 10% Fetal Bovine Serum (FBS) and 1% antibiotic (penicillin-streptomycin, 10000U m L)-1) The culture medium of (4). Wherein the cell culture under normal conditions is in the presence of 5% CO2And 20% of O2At 37 ℃ under humid conditions. The anoxic culture conditions are 5% CO2、1％O2And 94% N2Specifically, the cells may be, but not limited to, normal liver cells (L O2), liver cancer cells (Bel-7402), cervical cancer cells (He L a), and the like.
The synthesis steps of the platinum modified metal organic framework material MOF2-Pt-FA are as follows:
1) synthesis of MOF 2: aluminum chloride hexahydrate (AlCl)3· 6H2O), a mixture of cetyltrimethylammonium bromide (CTAB) and porphyrin (TCPP) was dissolved in water, reacted for 16h, and washed to give MOF 1. MOF1 and copper acetate (Cu (Ac))2·H2O) is reacted in N, N-Dimethylformamide (DMF), and the MOF2 particles are obtained by washing and drying for storage.
2) Synthesis of MOF 2-Pt: mixing MOF2 nanoparticles with chloroplatinic acid (H)2PtCl6) The mixture in water was reacted at room temperature. Next, an aqueous solution of sodium borohydride (NaBH) was added to the solution4) Then violently stirring to obtain MOF 2-Pt; .
3) Synthesis of MOF 2-Pt-FA: dissolving the MOF2-Pt in water, adding poly (ethylene glycol) -folic acid (FA-PEG-COOH), stirring at room temperature for 4h, and drying to obtain a product MOF 2-Pt-FA.
Specifically, the synthesis of MOF2 in step 1) comprises the following specific steps: mixing AlCl3·6H2A mixture of O (0.0125 mmol), cetyltrimethylammonium bromide (CTAB) (1 mmol) and TCPP (0.063 mmol) was dissolved in 5m L water and then added to a 20m L Teflon lined autoclave at 180 ℃ for 16 hours centrifugation to obtain purple nanoparticles, which were washed 3 times with DMF, H2O and acetone in turn, hereafter the product was named MOF 1. thereafter, MOF1 (170 ℃ under vacuum, overnight) (10 mg) and Cu (Ac)2·H2O (0.08 mmol) was dissolved in 2m L DMF and added to a 20m L Teflon lined autoclave and left at 100 ℃ for 24H2O and acetone 3 times. The obtained MOF2 particles were stored dry.
The specific synthesis steps of MOF2-Pt in the step 2) are as follows: mixing MOF2 nanoparticles (0.05 g) and H2PtCl6(20 mM, 1m L) mixture in 20m L water was stirred at room temperature for 1 h next, 2m L NaBH was added to the solution4（4 mg mL-1) And then stirred vigorously for 3 hours. Finally, the product was centrifuged and washed 3 times with water. This product is called MOF 2-Pt.
The synthesis of the MOF2-Pt-FA in the step 3) comprises the specific step of synthesizing 1m L MOF2-Pt nanoparticles (1 mgm L)-1) With 50. mu. L FA-PEG-COOH (5 mg m L)-1) Stirred at room temperature for 30 minutes. The obtained MOF2-Pt-FA was centrifuged and then redispersed in water for further use.
Specifically, the two-way enhanced photodynamic therapy nano drug MOF2-Pt-FA pair reduces GSH and is tested by specific adsorption: both MOF 1-Pt-FA and MOF2-Pt-FA produce large amounts of ROS under irradiation with light, while fluorescence is significantly reduced in the presence of GSH, indicating that GSH can scavenge the produced ROS. The fluorescence of the MOF2-Pt-FA is reduced-58%, significantly lower than that of MOF 1-Pt-FA (-17%), indicating that GSH suppresses a substantial consumption of ROS. Adsorption between CuII and GSH in MOF 2. The residual GSH concentration in the MOF 1-Pt-FA/MOF 2-Pt-FA supernatant after centrifugation was then measured using a commercial GSH kit, the GSH content in the MOF2-Pt-FA supernatant being lower than that of MOF 1-Pt-FA. All the above results show that MOF2-Pt-FA can reduce the content of GSH, thereby increasing the concentration of ROS.
Wherein, the MOF 1-Pt-FA and the MOF2-Pt-FA are irradiated at 638nm for 10 minutes.
The specific concentration of GSH is determined by standard curve obtained from the instruction in colorimetric microplate kit, and GSH and MOF 1/MOF 2 (20 or 50 μ g.m L)-1) After stirring for 30 minutes, the solution was centrifuged and the supernatant was used for GSH analysis according to the measurement protocol in the kit. The concentration of GSH required is the difference between total glutathione and oxidized glutathione.
Specifically, the test that the bidirectional enhanced photodynamic therapy nano-drug MOF2-Pt-FA has peroxidase-like activity: the catalytic activity of the MOF 2/MOF 2-Pt was determined by monitoring H in solution2O2Concentration, as determined by H2O2Ultraviolet absorption at 230 nm. H2O2A standard curve of concentration was obtained by absorbance of hydrogen peroxide at different concentrations (0-50 mM) at 230 nm MOF 2/MOF 2-Pt (50 μ gm L) every 10 minutes-1) Adding to a solution containing H2O2UV-vis spectra were recorded in PBS buffer (pH = 7.2) (20 mM).
The MOF2-Pt-FA not only has the function of reducing GSH in tumors, but also can decompose endogenous hydrogen peroxide well and relieve the tumor hypoxia environment.
The in vitro cell experiment comprises the following aspects: culturing cells under a proper condition, carrying out toxicity test on the cells by MOF2-Pt-FA, carrying out death-death double staining test, carrying out apoptosis test, carrying out cell uptake test, detecting adsorbed GSH, detecting active oxygen in the cells, and carrying out cell targeting and internalization test.
Has the advantages that: compared with the prior art, the invention has the following characteristics and advantages: the invention has simple principle, mild synthesis condition, low cost of raw materials, no need of any large-scale instrument and easy obtainment. The invention successfully designs the nano material MOF2-Pt-FA which can improve the PDT effect from multiple aspects. The synthesis of MOFs using the photosensitizer TCPP greatly reduces the problem of premature photosensitizer leakage. Cu (II) is taken as an active center, GSH in a tumor microenvironment can be effectively reduced, and then H in cells can be effectively decomposed by combining with surface-loaded Pt NPs2O2To produce oxygen that improves the hypoxic environment of the cell. PEG-FA modified MOF2-Pt not only enhances the biocompatibility of the material, but also is specific to tumor cells with folate receptors. This multimodal system provides a method to enhance PDT efficiency and facilitate the application of multifunctional MOFs for more effective cancer treatment.
Drawings
FIG. 1 shows a flow diagram based on platinum modified metal organic framework MOF2-Pt-FA as a bi-directionally enhanced photodynamic therapy;
FIG. 2 shows the characterization of nano-drugs prepared as bi-directionally enhanced photodynamic therapy based on platinum modified metal organic framework MOF 2-Pt-FA. Wherein FIG. 2 (A) is a TEM image of MOF2 (Cu-Al-MOF). FIG. 2 (B) is a TEM image of MOF2-Pt and the crystal lattice of Pt NPs observed under high resolution TEM. FIG. 2 (C) is an XRD pattern of the MOF2 and MOF2-Pt prepared and a simulation result of the MOF 2.
FIG. 3 shows the assay for GSH adsorption based on platinum modified metal organic framework material MOF2-Pt-FA as a nano-drug prepared by bi-directionally enhanced photodynamic therapy FIG. 3 (A) the fluorescence spectra of ROS probes (DCFH) treated with MOF 1-Pt-FA or MOF2-Pt-FA under 638nm light irradiation in the presence or absence of GSH (1 mM). FIG. 3 (B) is a graph showing comparison of 20 and 20 measured with a commercially available kitChange in the concentration of GSH in the supernatant after 50. mu.g/m L MOF 1-Pt-FA or MOF2-Pt-FA incubation C0Is the original concentration of GSH in solution, C1FIG. 3 (C) is the fluorescence response of MOF2-Pt-FA (50. mu.g/M L) after addition of various reactive substances, GSH (10. mu.M), Na2SO4（1 mM），Na2SO3（1 mM），Na2S2O3（1 mM）， Na2H2PO4（1 mM），NaHCO3（1 mM），Cys（100 nM），H2O2(1 mM) and Na2CO3（1 mM）。 F0Is the fluorescence intensity of MOF2-Pt-FA, and F is the fluorescence intensity of MOF2-Pt-FA incubated with the reactive species;
FIG. 4 shows the capacity of hydrogen peroxide decomposition of nano-drugs prepared based on platinum modified metal organic framework material MOF2-Pt-FA as a bidirectional enhanced photodynamic therapy (BIAS). The recorded H of MOF 2-FA and MOF2-Pt-FA of FIG. 4 (A) are reacted in PBS at pH =7.4 for different times2O2UV-vis spectrum (wavelength 230 nm). FIG. 4 (C) is the fluorescence spectrum of ROS probe (DCFH) incubated with MOF 2-FA or MOF2-Pt-FA for 10 min, with or without light irradiation. FIG. 4 (D) shows the presence or absence of H2O2In the case of (1), in N2Incubated with MOF 2-FA or MOF2-Pt-FA under an atmosphere of light irradiation1O2Photodegradation rate of probe (DPBF). A. the0Is the initial absorbance of the material, H2O2The concentration of (a) is 100. mu.M.
FIG. 5 shows the evaluation of photodynamic therapy effect of nano-drugs prepared based on platinum-modified metal organic framework material MOF2-Pt-FA as a bidirectional enhanced photodynamic therapy in the atmospheric oxygen of FIG. 5 (A) under laser irradiation (638 nm, 1.0W cm)-2) Bel-7402 cells were subjected to in vitro PDT conditions and FIG. 5 (B) under hypoxic conditions after incubation with various concentrations of MOF1, MOF2, MOF2-Pt and MOF 2-Pt-FA. Flow cytometry analysis of FDA (live/green) and PI (dead/red) co-stained cells fig. 5 (C) and fluorescence images.
Detailed Description
The present invention is further illustrated by the following specific examples and the accompanying drawings, and it should be noted that, for those skilled in the art, variations and modifications can be made without departing from the principle of the present invention, and these should also be construed as falling within the scope of the present invention.
Reagents and instruments used in this experiment:
tetrahydro (4-carboxyphenyl) porphyrin (TCPP) was ordered from HWRK Chemical (Beijing, China). Chloroplatinic acid (H)2PtCl6) Copper acetate (Cu (Ac))2) 1, 3-Diphenylisobenzofuran (DPBF), Propidium Iodide (PI) and calcein AM were obtained from Sigma-Aldrich (USA). N, N' -Dimethylformamide (DMF), dimethyl sulfoxide (DMSO), sodium sulfate (Na)2SO4) And sodium sulfite (Na)2SO3) Purchased from national drug-controlled chemical reagents, ltd (shanghai, china). The GSH/GSSG assay kit was purchased from Beyotime Biotechnology (Shanghai, China). 2', 7' -dichlorodihydrofluorescein diacetate (DCFH-DA) was purchased from Dalian America Biotechnology Ltd, China Dalian. (folate) -poly (ethylene glycol) (FA-PEG-COOH, Mw = 10 kDa) was obtained from postcure Biotechnology (shanghai, china). Deionized water was prepared with a Milli-Q purification system at a resistivity of 18.2M Ω.
The PBS buffer solution in the embodiment of the invention is: 137 mM NaCl, 10mM NaH2PO4、2.7 mM KCl、2mM KH2PO4，pH 7.2。
Example 1: synthesis of MOF2
Mixing AlCl3·6H2A mixture of O (0.0125 mmol), cetyltrimethylammonium bromide (CTAB) (1 mmol) and TCPP (0.063 mmol) was dissolved in 5m L water and then added to a 20m L Teflon lined autoclave at 180 ℃ for 16 hours centrifugation to obtain purple coloured nanoparticles, washed 3 times with DMF, H2O and acetone in sequence, hereafter the product was named MOF 1. thereafter, MOF1 (170 ℃ under vacuum, overnight) (10 mg) and Cu (Ac)2·H2O (0.08 mmol) in 2m L DMF was addedAdd to a 20m L Teflon lined autoclave and let stand at 100 ℃ for 24H the product was collected by centrifugation and washed sequentially with DMF, H2O and acetone 3 times. The obtained MOF2 particles were stored dry.
FIG. 2 (A) shows a TEM image of the synthesized nanoparticle MOF2, the size of the nanoparticle MOF2 being 100-200 nm; figure 2 (C) shows XRD images as well as simulated images of the synthesized nanoparticle MOF 2.
Example 2: synthesis of MOF2-Pt
The specific steps of synthesis of MOF2-Pt are to mix MOF2 nanoparticles (0.05 g) and H2PtCl6(20 mM, 1m L) mixture in 20m L water was stirred at room temperature for 1 h next, 2m L NaBH was added to the solution4（4 mg mL-1) And then stirred vigorously for 3 hours. Finally, the product was centrifuged and washed 3 times with water. This product is called MOF 2-Pt.
FIG. 2 (B) shows TEM images and high resolution lattice images of the synthesized nanoparticles MOF2-Pt, with platinum nanoparticles of 2-5 nm in size; FIG. 2 (C) shows an XRD pattern of the synthesized nanoparticle MOF 2-Pt.
Example 3: synthesis of MOF2-Pt-FA
1m L MOF2-Pt nanoparticles (1 mg m L)-1) With 50. mu. L FA-PEG-COOH (5 mg m L)-1) Stirred at room temperature for 30 minutes. The obtained MOF2-Pt-FA was centrifuged and then redispersed in water for further use.
Example 4: MOF2-Pt-FA adsorption test on GSH
The amount of ROS induced by MOF 1/MOF 2 in the absence or presence of GSH (1 mM) was measured by the fluorescent probe 2, 7-Dichlorofluorescein (DCFH). The mixture was irradiated with 638nm light at 1W cm-2Is irradiated for 10 minutes. Immediately after irradiation, the solution was centrifuged and the fluorescence of the supernatant was measured to estimate the ROS produced.
The total concentration of glutathione and oxidized glutathione was determined according to a standard curve obtained according to the instructions in the colorimetric microplate assay kit GSH and MOF 1/MOF 2 (20 or 50. mu. g m L)-1) After stirring for 30 minutesThe solution was centrifuged and the supernatant was then used for GSH analysis according to the manufacturer's protocol. The concentration of GSH we require is the difference between total glutathione and oxidized glutathione.
FIG. 3 shows a MOF 2-Pt-FA-based assay for GSH adsorption FIG. 3 (A) fluorescence spectra of ROS probes (DCFH) treated with MOF 1-Pt-FA or MOF2-Pt-FA in the presence or absence of GSH (1 mM) under 638nm light irradiation FIG. 3 (B) is the change in concentration of GSH in supernatant after incubation with 20 or 50 μ g/m L MOF 1-Pt-FA or MOF2-Pt-FA measured with a commercial kit0Is the original concentration of GSH in solution, C1Is the concentration of GSH in the solution after addition of the materials FIG. 3 (C) is the fluorescence response of MOF2-Pt-FA (50. mu.g/M L) after addition of various reactive substances, GSH (10. mu.M), Na2SO4（1mM），Na2SO3（1 mM），Na2S2O3（1 mM）， Na2H2PO4（1 mM），NaHCO3（1 mM），Cys（100 nM），H2O2(1 mM) and Na2CO3（1 mM）。 F0Is the fluorescence intensity of MOF2-Pt-FA, and F is the fluorescence intensity of MOF2-Pt-FA incubated with the reactive species; tests prove that the MOF2-Pt-FA can not only reduce the concentration of the GSH, but also can specifically adsorb the GSH.
Example 4: MOF2-Pt-FA peroxidase activity detection
The catalytic activity of the MOF 2/MOF 2-Pt was determined by monitoring H in solution2O2Concentration, as determined by H2O2Ultraviolet absorption at 230 nm. H2O2A standard curve of concentration was obtained by absorbance of hydrogen peroxide at 230 nm at different concentrations (0-50 mM.) MOF 2/MOF 2-Pt (50 μ g m L) was added every 10 minutes-1) Adding to a solution containing H2O2UV-vis spectra were recorded in PBS buffer (pH = 7.2) (20 mM).
After reacting MOF 2-FA in fig. 4 (a) and MOF2-Pt-FA in fig. 4 (B) for different times in PBS pH =7.4, UV-vis spectra (wavelength 230 nm) of H2O2 were recorded.
Example 5: detection of active oxygen generation capability of MOF2-Pt-FA
To simulate an anoxic environment, MOF 2/MOF 2-Pt (10 μ g m L)-1) And 5. mu. L DPBF/ethanol solution (10 mM) with or without H2O2Ventilation (100 μ M) was performed. N is a radical of2For 30 minutes. Then at 638nm at 1 Wcm-2The solution was irradiated for 10 minutes. A characteristic uv-vis absorption spectrum of DPBF was obtained to determine ROS generation.
FIG. 4 (C) fluorescence spectra of ROS probe (DCFH) incubated with MOF 2-FA or MOF2-Pt-FA for 10 min with or without light irradiation. FIG. 4 (D) with or without H2O2In the case of (1), in N2Incubated with MOF 2-FA or MOF2-Pt-FA under an atmosphere of light irradiation1O2Photodegradation rate of probe (DPBF). A. the0Is the initial absorbance of the material, H2O2The concentration of (a) is 100. mu.M.
Example 6: MOF2-Pt-FA photodynamic therapy effect evaluation
Bel-7402 cells were cultured at 5 × 104Cells/well density seeded in 96-well plates for 24 hours in fresh complete medium at 5% CO2And 95% air at 37 ℃. PBS, MOF1, MOF2-Pt-FA were added to the plates separately and incubated for 4 hours. The plate was then irradiated with a 638nm laser (1W cm)-2) Irradiation for 10 min then MTT solution (200. mu. L, 1 mg m L)-1) Added to each well at 37% 5% CO2After 4 hours of incubation in 95% air, the MTT solution was aspirated and 150 μ L dmso was added to each well.
FIG. 5 (A) Normal oxygen laser irradiation (638 nm, 1.0W cm)-2) Bel-7402 cells were subjected to in vitro PDT conditions and FIG. 5 (B) under hypoxic conditions after incubation with various concentrations of MOF1, MOF2, MOF2-Pt and MOF 2-Pt-FA.
Example 6: MOF2-Pt-FA cell flow analysis
Bel-7402 cells were cultured at 5 × 104Cells/well density seeded in 96-well plates for 24 hours in fresh complete medium at 5% CO2And 95% air at 37 ℃. PBS, MOF1, MOF2-Pt-FA were added to the plates separately and incubated for 4 hours. The plate was then irradiated with a 638nm laser (1W cm)-2) The irradiation was carried out for 10 minutes. After a further 24 hours of incubation, a quantitative assessment of cell viability was performed by MTT assay as described above.
The Annexin V-FITC/PI apoptosis detection kit is used for monitoring apoptosis through a flow cytometer.
FIG. 5 (C) flow cytometric analysis and fluorescence images of FDA (live/green) and PI (dead/red) co-stained cells.
The above-mentioned embodiments are merely preferred embodiments of the present invention, and should not be construed as limiting the present invention, and the scope of the present invention should be defined by the claims, and equivalents including technical features of the claims, i.e., equivalent modifications within the scope of the present invention.
Claims (10)
1. Application of platinum modified metal organic framework material MOF2-Pt-FA in preparation of drugs for treating tumors.
2. Use according to claim 1, characterized in that: the platinum modified metal organic framework material MOF2-Pt-FA is obtained by using bivalent copper ions as an active center and porphyrin as a ligand, depositing platinum nanoparticles on the surface of the material in situ, and then wrapping the material by using high polymer PEG-FA.
3. Use according to claim 2, characterized in that: the particle size of the platinum modified metal organic framework material MOF2-Pt-FA is 80-200 nm.
4. Use according to claim 2, characterized in that: the particle size of the platinum nano-particles is 2-10 nm.
5. The use according to claims 1 to 4, wherein the platinum modified metal organic framework material MOF2-Pt-FA is prepared as follows:
1) synthesis of MOF 2: dissolving aluminum chloride hexahydrate, hexadecyl trimethyl ammonium bromide and porphyrin in water for reaction to obtain MOF 1; mixing MOF1, copper acetate and N, N-dimethylformamide to obtain MOF2 particles;
2) synthesis of MOF 2-Pt: mixing the MOF2 nano particles with an aqueous solution of chloroplatinic acid, adding an aqueous solution of sodium borohydride, and stirring to obtain MOF 2-Pt;
3) synthesis of MOF 2-Pt-FA: dissolving MOF2-Pt in water, adding poly (ethylene glycol) -folic acid, stirring, and drying to obtain the product MOF 2-Pt-FA.
6. Use according to claim 5, characterized in that: in the step 1), the mass of the aluminum chloride hexahydrate is 0.2-0.5g, the mass of the hexadecyl trimethyl ammonium bromide is 20-100mg, the mass of the porphyrin is 0.5-1g, and the mass of the copper acetate is 0.01-0.05 g; the volume of N, N-dimethylformamide is 1-5 ml.
7. The use according to claim 5, wherein the mass of the MOF2 nanoparticles in step 2) is 0.01-0.05g, the mass of the chloroplatinic acid in the aqueous solution of the chloroplatinic acid is 0.01-0.05g, and the concentration of the aqueous solution of sodium borohydride is 2-5mg m L-1。
8. Use according to claim 5, characterized in that: in the step 3), the mass of the MOF2-Pt is 10-100mg, and the mass of the poly (ethylene glycol) -folic acid is 10-100 mg.
9. Use according to claim 5, characterized in that: the reaction temperature for synthesizing the MOF1 in the step 1) is 150-200 ℃, and the reaction time is 15-30 hours.
10. The use according to claim 5, wherein the concentration of the solution of the platinum modified metal organic framework material MOF2-Pt-FA is 20-100 μ g m L-1。
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