CN114681611B - Poly 3-thiopheneacetic acid modified PCN-224 composite material and preparation method and application thereof - Google Patents
Poly 3-thiopheneacetic acid modified PCN-224 composite material and preparation method and application thereof Download PDFInfo
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- RCNOGGGBSSVMAS-UHFFFAOYSA-N 2-thiophen-3-ylacetic acid Chemical compound OC(=O)CC=1C=CSC=1 RCNOGGGBSSVMAS-UHFFFAOYSA-N 0.000 title claims abstract description 60
- 239000002131 composite material Substances 0.000 title claims abstract description 34
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- 238000003756 stirring Methods 0.000 claims description 17
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- RKCAIXNGYQCCAL-UHFFFAOYSA-N porphin Chemical compound N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 RKCAIXNGYQCCAL-UHFFFAOYSA-N 0.000 claims description 4
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- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- HHDUMDVQUCBCEY-UHFFFAOYSA-N 4-[10,15,20-tris(4-carboxyphenyl)-21,23-dihydroporphyrin-5-yl]benzoic acid Chemical compound OC(=O)c1ccc(cc1)-c1c2ccc(n2)c(-c2ccc(cc2)C(O)=O)c2ccc([nH]2)c(-c2ccc(cc2)C(O)=O)c2ccc(n2)c(-c2ccc(cc2)C(O)=O)c2ccc1[nH]2 HHDUMDVQUCBCEY-UHFFFAOYSA-N 0.000 description 2
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
- A61K41/0076—PDT with expanded (metallo)porphyrins, i.e. having more than 20 ring atoms, e.g. texaphyrins, sapphyrins, hexaphyrins, pentaphyrins, porphocyanines
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
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- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
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- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0054—Macromolecular compounds, i.e. oligomers, polymers, dendrimers
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Abstract
The invention discloses a poly-3-thiopheneacetic acid modified PCN-224 composite material, and a preparation method and application thereof. The preparation method of the poly 3-thiopheneacetic acid modified PCN-224 composite material comprises the following steps: and mixing and uniformly dispersing the PCN-224 and the PTAA in a solvent, and then centrifuging, washing and drying the mixture to obtain the poly 3-thiopheneacetic acid modified PCN-224 composite material. According to the invention, the dispersibility can be improved by coating the poly-3-thiopheneacetic acid on the surface of the PCN-224, and the obtained poly-3-thiopheneacetic acid modified PCN-224 composite material has excellent biocompatibility, lower biotoxicity and very high killing rate on tumor cells under illumination conditions.
Description
Technical Field
The invention relates to the technical field of medical materials, in particular to a poly-3-thiopheneacetic acid modified PCN-224 composite material, and a preparation method and application thereof.
Background
Despite significant advances in traditional tumor treatment methods (e.g., surgery, radiation therapy, and chemotherapy), cancer remains the first killer in humans. Novel tumor treatment means: photodynamic therapy (PDT) attracts the eyes of researchers. PDT has unique advantages over traditional tumor treatment approaches: the wound is small, the treatment can be repeated, the selectivity is high, and the medicine can be combined with other treatment means for treatment.
In brief, PDT is a non-invasive topical tumor treatment, in a tissue that is common to photosensitizers, light and oxygen, the photosensitizers are converted from a ground state to an excited state by excitation of light of a specific wavelength, and the surrounding oxygen is converted to Reactive Oxygen Species (ROS) by the energy released by the photosensitizers. ROS has certain cytotoxicity, can inhibit cell growth, promote apoptosis, damage tumor blood vessels, stimulate thromboxane release, and cause tumor tissue infarction. Thus, PDT can selectively kill tumor cells due to the dependence on light and photosensitizers, so that specific sites where tumors grow can be irradiated with laser light, killing tumor cells while protecting surrounding normal tissues.
PCN-224 is prepared from meso-tetra (4-carboxyphenyl) porphin as ligand and Zr 4+ MOFs constructed through coordination have the characteristics of rigid structure, large specific surface area, high porosity, excellent photosensitivity, thermal stability and the like, and are often used for photodynamic therapy of tumors. At present, the application of the compound to tumor treatment and the application of the compound as a drug carrier are studied, but the compound is easy to aggregate and has high biotoxicity, so that the compound is always a difficult point to be overcome in the field of photodynamic therapy.
Disclosure of Invention
The invention aims to overcome the technical defects, and provides a poly-3-thiopheneacetic acid modified PCN-224 composite material, a preparation method and application thereof, and solves the technical problems of easiness in aggregation and higher biotoxicity of PCN-224 in the prior art.
The first aspect of the invention provides a preparation method of a poly 3-thiopheneacetic acid modified PCN-224 composite material, comprising the following steps:
PCN-224 and poly-3-thiopheneacetic acid (PTAA) are mixed and uniformly dispersed in a solvent, and then the mixture is centrifuged, washed and dried to obtain the poly-3-thiopheneacetic acid modified PCN-224 composite material.
The second aspect of the invention provides a poly 3-thiopheneacetic acid modified PCN-224 composite material, which is obtained by the preparation method of the poly 3-thiopheneacetic acid modified PCN-224 composite material provided by the first aspect of the invention.
In a third aspect, the invention provides an application of the poly 3-thiopheneacetic acid modified PCN-224 composite material, wherein the poly 3-thiopheneacetic acid modified PCN-224 composite material is applied to serving as a photosensitizer in tumor photodynamic therapy.
Compared with the prior art, the invention has the beneficial effects that:
according to the invention, the dispersibility can be improved by coating the poly-3-thiopheneacetic acid on the surface of the PCN-224, and the obtained poly-3-thiopheneacetic acid modified PCN-224 composite material has excellent biocompatibility, lower biotoxicity and very high killing rate on tumor cells under illumination conditions.
Drawings
FIG. 1 is a graph showing absorption spectra at 300 to 800nm of PTAA, PCN-224 (P) and PCN-224@PTAA (PP) obtained in example 1 of the present invention;
FIG. 2 is a graph showing the analysis of the results of cytotoxicity test on PCN-224 (P) and PCN-224@PTAA (PP) obtained in example 1 of the present invention; wherein, (1) is a HeLa cell, and (2) is a U14 cell;
FIG. 3 is an analysis chart of the cytotoxicity test assay results of PCN-224 (P) and PCN-224@PTAA (PP) obtained in example 1 of the present invention; wherein, (1) is a HeLa cell, and (2) is a U14 cell;
FIG. 4 is a fluorescence imaging of intracellular co-localization of PCN-224 (P) and PCN-224@PTAA (PP) obtained in example 1 of the present invention with cell membrane and nucleus;
FIG. 5 is a graph showing the effect of cell uptake of PCN-224 (P) and PCN-224@PTAA (PP) obtained in example 1 of the present invention; wherein, (A) is a bar graph, and (B) is a line graph.
Detailed Description
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
The first aspect of the invention provides a preparation method of a poly 3-thiopheneacetic acid modified PCN-224 composite material, comprising the following steps:
PCN-224 and poly-3-thiopheneacetic acid (PTAA) are mixed and uniformly dispersed in a solvent, and then the mixture is centrifuged, washed and dried to obtain the poly-3-thiopheneacetic acid modified PCN-224 composite material (named as PCN-224@PTAA or PP).
In the present invention, the particle size of PCN-224 is less than 500nm, more preferably 50 to 300nm, still more preferably 50 to 150nm.
In the invention, the mass ratio of PTAA to PCN-224 is 1: (10-100), further 1: (50-70), further 1: (55-60).
In the present invention, the solvent is a mixed solvent of water and an organic solvent. Further, the organic solvent is dimethyl sulfoxide (DMSO); further, the volume ratio of water to organic solvent is (30-60): 1.
in the invention, the dosage ratio of PCN-224 to solvent is 1mg: (5-20) mL.
In the invention, the step of uniformly mixing and dispersing PCN-224 and poly-3-thiopheneacetic acid in a solvent comprises the following steps:
adding PCN-224 into water and uniformly dispersing to obtain PCN-224 solution; wherein the concentration of the PCN-224 solution is 0.1-10 mM, more 0.5-2 mM, and still more 1mM;
dissolving PTAA in an organic solvent to obtain a PTAA solution; wherein the concentration of PTAA solution is 0.1-10 mg/mL, more 0.5-2 mg/mL, still more 1mg/mL.
Uniformly mixing the PTAA solution and the PCN-224 solution to obtain a mixture; wherein, PTAA solution and PCN-224 solution are uniformly mixed by stirring for 2-24 hours, more 3-10 hours and still more 4-6 hours.
In the invention, the rotation speed of the centrifuge is 10000-15000 rpm, and further 12000rpm in the process of centrifuging, washing and drying the mixture; the centrifugation time is 10-30 min, and further 20min; washing solvents DMSO and water according to 1:99 volume ratio; the drying mode is freeze drying.
In some preferred embodiments of the invention, PCN-224 is obtained by: meso-tetra (4-carboxyphenyl) porphin (H 2 TCPP), zirconium oxychloride octahydrate (ZrOCl) 2 ·8H 2 O) and Benzoic Acid (BA) in dimethylformamideHeating and stirring in (DMF) at 80-100 deg.c for 3-6 hr, centrifuging, washing and drying to obtain PCN-224. Wherein the dosage ratio of the meso-tetra (4-carboxyphenyl) porphine, the zirconium oxychloride octahydrate, the benzoic acid and the dimethylformamide is 0.1-5 mg: 1-5 mg: 10-50 mg:1mL; further 1mg:3mg:28mg:1mL.
In some preferred embodiments of the invention, PTAA is obtained by: 3-thiopheneacetic acid, anhydrous FeCl 3 And anhydrous CH 2 Cl 2 After mixing, stirring and reacting for 3-5 h at 20-30 ℃ under the protection of nitrogen; then distilled under reduced pressure to remove CH 2 Cl 2 Ethanol is added, and stirred and reacted for 3 to 5 hours at the temperature of 20 to 30 ℃; filtering, discarding filtrate, washing filter cakes with hydrochloric acid and ethanol respectively, and refluxing in ethanol at 70-90 ℃ for 1-3 hours; filtering, and vacuum drying filter cake overnight; dissolving the obtained reddish brown powder in NaOH solution, stirring for 12-36 hours at 90-110 ℃, and centrifuging to remove insoluble matters; adding concentrated HCl into the supernatant, stirring at normal temperature for 8-12 h, standing for 24-72 h to enable the supernatant to be precipitated and aged, pouring out the supernatant, adding distilled water, micro-filtering, washing a filter cake with water and ethanol, and drying in vacuum to obtain the poly-3-thiopheneacetic acid. Wherein, anhydrous FeCl 3 The molar ratio of the catalyst to 3-thiopheneacetic acid is (4-6), wherein 1 is further 5:1, a step of; 3-thiopheneacetic acid and anhydrous CH 2 Cl 2 The dosage ratio of (2) is 1g: (100-140) mL; in the stirring reaction process, the dosage ratio of 3-thiopheneacetic acid to ethanol is 1g: (100-140) mL; in the reflux process, the dosage ratio of 3-thiopheneacetic acid to ethanol is 1g: (100-120) mL; the concentration of the sodium hydroxide solution is 1-3 mol/L, and the dosage ratio of the 3-thiopheneacetic acid to the sodium hydroxide solution is 1g: (100-140) mL.
The second aspect of the invention provides a poly 3-thiopheneacetic acid modified PCN-224 composite material, which is obtained by the preparation method of the poly 3-thiopheneacetic acid modified PCN-224 composite material provided by the first aspect of the invention.
In a third aspect, the invention provides an application of the poly 3-thiopheneacetic acid modified PCN-224 composite material, wherein the poly 3-thiopheneacetic acid modified PCN-224 composite material is applied to serving as a photosensitizer in tumor photodynamic therapy.
Example 1
Preparation of PCN-224 (P): meso-tetra (4-carboxyphenyl) porphin (H 2 TCPP) 100mg, zirconium oxychloride octahydrate (ZrOCl) 2 ·8H 2 O) 300mg and 2.8g of Benzoic Acid (BA) were dissolved in a 250mL round bottom flask containing 100mL of DMF, stirred under heating at 300rpm in an oil bath at 90℃for 5h, PCN-224 nanoparticles (particle size about 70 nm) were collected by centrifugation, washed 3 times with DMF and ethanol, and the final product was lyophilized to a powder and stored at 4℃protected from light.
Preparation of PTAA: into a 250mL eggplant-shaped bottle, 0.71g (5 mmol) of 3-thiopheneacetic acid, 4.06g (25 mmol) of anhydrous FeCl were successively added 3 (FeCl 3 Monomer molar ratio 5:1) and 100mL anhydrous CH 2 Cl 2 Stirring for 4h at normal temperature (25 ℃) under the protection of nitrogen; then the majority of CH is removed by distillation under reduced pressure 2 Cl 2 100mL of ethanol is added and stirred for 4 hours at 25 ℃; filtering, discarding filtrate, washing filter cakes with 100mL of 1mol/L hydrochloric acid and 100mL of ethanol respectively, and refluxing in 80mL of ethanol at 80 ℃ for 2 hours; filtering, and vacuum drying the filter cake at 30deg.C overnight; dissolving the obtained reddish brown powder in 100mL of 2mol/L NaOH solution, stirring at 100 ℃ for 24 hours, and centrifuging to remove insoluble matters; adding 100mL of concentrated HCl into the supernatant, stirring at normal temperature for 10h, standing for 48h to enable the supernatant to be precipitated and aged, gently pouring the supernatant, adding 50mL of secondary distilled water, micro-filtering, washing a filter cake with water and ethanol, and then drying the filter cake in vacuum at 40 ℃ until the filter cake is dry to obtain blue-black poly 3-thiopheneacetic acid powder.
Preparation of PCN-224@PTAA (PP): 14.54mg of the dried PCN-224 powder was suspended in 10mL of water and sonicated for 30min to give a 1mM PCN-224 solution; 1mg of PTAA is dissolved in 1mL of DMSO to obtain a PTAA solution with a concentration of 1 mg/mL; 0.25mL of PTAA solution was stirred into the PCN-224 solution with additional stirring, stirring was continued for 5 hours, and then the mixture was centrifuged (12000 rpm,20 min) and washed three times with DMSO/water (v/v: 1/99) to eliminate excess PTAA ligand, and freeze-dried to give PCN-224@PTAA (PP).
Referring to FIG. 1, FIG. 1 is a graph showing absorption spectra of PTAA, PCN-224 (P) and PCN-224@PTAA (PP) obtained in example 1 of the present invention at 300-800 nm. As can be seen from fig. 1, although PTAA has good biocompatibility and is non-toxic to cells, PTAA has no absorption peak at 650-660 nm, which cannot be photoexcited, indicating that PTAA alone has no photodynamic effect; the PCN-224 (P) has weak absorption peaks at 650-660 nm, which indicates that the PCN-224 (P) has a certain photodynamic effect; the PCN-224@PTAA (PP) has a strong absorption peak at 650-660 nm, and can be better excited by light, so that the PCN-224@PTAA (PP) has a better photodynamic effect.
Test examples
1. Cytotoxicity test
Hela cells and U14 cells were cultured in DMEM medium containing 10% fetal bovine serum by volume fraction and CO by volume fraction of 5%, respectively 2 The cells were cultured at 37℃in an atmosphere, and then the cultured cells were inoculated in 96-well plates at about 8000 cells per well and incubated for 20 hours. The drugs prepared in example 1 were added to 96-well plates at different concentrations, incubated for 4 hours, replaced with fresh medium, and incubated for 24 hours for further MTT assay. The test results are shown in FIG. 2.
As can be seen from fig. 2, the biocompatibility of PP is significantly better than that of P, which indicates that the poly-3-thiopheneacetic acid is favorable for improving the biocompatibility of PCN-224 after modification.
2. Cytotoxicity test
Hela cells and U14 cells were cultured in DMEM medium containing 10% fetal bovine serum by volume fraction and CO by volume fraction of 5%, respectively 2 The cells were cultured at 37℃in an atmosphere, and then the cultured cells were inoculated in 96-well plates at about 5000 cells per well and incubated for 20 hours. The drugs prepared in example 1 were added to 96-well plates at different concentrations, incubated for 4 hours, replaced with fresh medium, subjected to 658nm light treatment, and incubated with serum for 24 hours, followed by MTT assay. The test results are shown in FIG. 3.
As can be seen from fig. 3, PP has a greater cell killing power than P, indicating that modification with poly-3-thiopheneacetic acid is beneficial to increasing phototoxicity of PCN-224.
3. Cell uptake efficacy test
PCN-224 has red fluorescence, so the nanoparticle itself can be used for fluorescence detection in cell uptake experiments. The cell membrane was labeled with DIO dye and the nucleus was labeled with DAPI dye. In order to directly observe the uptake of the nanoparticles in the cells, a laser scanning confocal microscope (CLSM) is selected to observe the uptake of the nanoparticles by the cells. Meanwhile, the relationship between the uptake capacity of the cells on the nano particles and the concentration of the nano particles in a certain concentration range is detected by using a flow cytometer.
For CLSM imaging, sterile cell culture slides were first placed in 24-well plates, and then Hela cells were cultured in 24-well plates at a density of 8 tens of thousands per well for 20h, allowing cells to grow on the slides in an adherent manner. After the completion of the culture, the original medium was aspirated by a pipette, and 5. Mu.g/mL of PCN-224 and PTAA@PCN-224 diluted with the serum-free medium were added, respectively, and the culture was continued for 4 hours. The culture was then aspirated and the cells were washed three times with PBS to remove some of the nanoparticles that were not taken up by the cells. And adding 300 mu L of DIO working solution into each hole for further incubation for 15min, washing cells with PBS for three times after the incubation is completed to remove redundant DIO dye solution, fixing the glass slide with 4% paraformaldehyde for 15min, taking out the glass slide, washing the cell slide with PBS for three times, reversely buckling the cell slide on a glass slide with 10 mu L of anti-fluorescence quenching sealing solution containing DAPI dropwise, and finally observing by using a laser scanning confocal microscope for imaging, wherein the test result is shown in figure 4.
For flow cytometry assays, hela cells were first incubated in 24 well plates at a density of 10 tens of thousands per well for 20h, the original medium was aspirated with a pipette, nanoparticles were diluted with serum-free medium at a series of different concentrations (5, 10, 20 μg/mL) and added to the 24 well plates, incubated for 4 hours, the medium was aspirated, and the cells were washed three times with PBS to remove some of the non-cellular nanoparticles, digested with 300 μl pancreatin per well, and then stopped with DMEM medium containing fetal bovine serum and aspirated into 1.5mL centrifuge tubes for centrifugation. After centrifugation, the supernatant was discarded, and then 1ml of LPBS was added for centrifugal washing. Then 200 microliters of PBS was added to each of the tubes, and the test was performed in an ice bath. Finally, the intensity of red fluorescence in the cells is detected by a flow cytometer, and the mean percp-A value is read, and the test result is shown in FIG. 5.
FIG. 4 is a fluorescence image of the intracellular co-localization of PCN-224 (P) and PCN-224@PTAA (PP) obtained in example 1 of the present invention with cell membrane and nucleus. As can be seen from FIG. 4, the PCN-224@PTAA (PP) obtained in example 1 of the present invention was used for fluorescence detection in cell uptake experiments, and the red fluorescence in cells was significantly enhanced.
FIG. 5 is a graph showing the effect of cell uptake of PCN-224 (P) and PCN-224@PTAA (PP) obtained in example 1 of the present invention. As can be seen from FIG. 5, the PCN-224@PTAA (PP) of the invention has better dispersibility and is easy to be swallowed by cells, and compared with the PCN-224, the PCN-224@PTAA is co-incubated with Hela cells under the same conditions, and the endocytosis of the PCN-224@PTAA is about twice that of the PCN-224.
Compared with the prior art, the invention has the beneficial effects that:
(1) The PCN-224@PTAA synthesized by the method has a large specific surface area, has a particle size of about 110nm, and is very suitable for biological experiments;
(2) The PCN-224@PTAA provided by the invention has better dispersibility and is easy to swallow by cells, and compared with the PCN-224, the PCN-224@PTAA is incubated with Hela cells under the same conditions, and the endocytosis of the PCN-224@PTAA is about twice that of the PCN-224;
(3) The PCN-224@PTAA has lower biotoxicity, and the toxicity of the metal ions of the PCN-224 in normal tissues is reduced due to the coating of the PTAA;
(4) The PCN-224@PTAA prepared by the method and the anti-tumor research thereof show that the PCN- @PTAA has good biocompatibility, the killing rate of the PCN-224@PTAA to tumor cells under the condition of low dose of illumination reaches more than 80%, and the killing rate of the PCN-224@PTAA under the condition of darkness is lower than 10%.
(5) The invention provides a material with fluorescent effect, which is convenient for positioning and tracking in vivo fluorescent imaging;
(6) The PCN-224@PTAA has good thermal stability and photostability, and is easy to administer for a small number of times and repeatedly treat by photodynamic therapy;
(7) The PCN-224@PTAA is simple and safe in synthesis steps, and the dosage of the organic reagent used in the process is small, so that the pollution to the environment is reduced, and the method is an effective method for synthesizing a novel photosensitizer.
The above-described embodiments of the present invention do not limit the scope of the present invention. Any other corresponding changes and modifications made in accordance with the technical idea of the present invention shall be included in the scope of the claims of the present invention.
Claims (9)
1. The preparation method of the poly 3-thiopheneacetic acid modified PCN-224 composite material is characterized by comprising the following steps of:
mixing PCN-224 and poly-3-thiopheneacetic acid in a solvent and uniformly dispersing, and then centrifuging, washing and drying the mixture to obtain a poly-3-thiopheneacetic acid modified PCN-224 composite material; wherein, the mass ratio of the poly 3-thiopheneacetic acid to the PCN-224 is 1: (10-100).
2. The method for preparing a poly 3-thiopheneacetic acid modified PCN-224 composite material according to claim 1, wherein the particle size of PCN-224 is less than 500nm.
3. The method for preparing the poly-3-thiopheneacetic acid modified PCN-224 composite material according to claim 1, wherein the solvent is a mixed solvent formed by water and dimethyl sulfoxide.
4. The method for preparing the poly 3-thiopheneacetic acid modified PCN-224 composite material according to claim 1, wherein the step of mixing and dispersing the PCN-224 and the poly 3-thiopheneacetic acid uniformly in the solvent comprises the following steps:
adding PCN-224 into water and uniformly dispersing to obtain PCN-224 solution;
dissolving poly 3-thiopheneacetic acid in dimethyl sulfoxide to obtain a poly 3-thiopheneacetic acid solution;
and uniformly mixing the poly 3-thiopheneacetic acid solution and the PCN-224 solution to obtain a mixture.
5. The method for preparing the poly-3-thiopheneacetic acid modified PCN-224 composite material according to claim 4, wherein the poly-3-thiopheneacetic acid solution and the PCN-224 solution are uniformly mixed by stirring for 2-24 hours.
6. The method for preparing the poly 3-thiopheneacetic acid modified PCN-224 composite material according to claim 1, wherein the PCN-224 is obtained by the following steps: dissolving meso-tetra (4-carboxyphenyl) porphin, zirconium oxychloride octahydrate and benzoic acid in dimethylformamide, heating and stirring for 3-6 hours at 80-100 ℃, and then centrifuging, washing and drying to obtain PCN-224.
7. The method for preparing the poly 3-thiopheneacetic acid modified PCN-224 composite material according to claim 1, wherein the poly 3-thiopheneacetic acid is obtained by the following steps: 3-thiopheneacetic acid, anhydrous FeCl 3 And anhydrous CH 2 Cl 2 After mixing, stirring and reacting for 3-5 hours at 20-30 ℃ under the protection of nitrogen; then distilled under reduced pressure to remove CH 2 Cl 2 Ethanol is added, and stirring reaction is carried out for 3-5 hours at 20-30 ℃; filtering, discarding filtrate, washing filter cakes with hydrochloric acid and ethanol respectively, and refluxing in ethanol at 70-90 ℃ for 1-3 hours; filtering, and vacuum drying filter cake overnight; dissolving the obtained reddish brown powder in NaOH solution, stirring for 12-36 hours at 90-110 ℃, and centrifuging to remove insoluble matters; adding concentrated HCl into the supernatant, stirring at normal temperature for 8-12 h, standing for 24-72 h to enable the supernatant to be precipitated and aged, pouring out the supernatant, adding distilled water, micro-filtering, washing a filter cake with water and ethanol, and drying in vacuum to obtain the poly-3-thiopheneacetic acid.
8. The poly 3-thiopheneacetic acid modified PCN-224 composite material is characterized in that the poly 3-thiopheneacetic acid modified PCN-224 composite material is obtained by the preparation method of the poly 3-thiopheneacetic acid modified PCN-224 composite material in any one of claims 1-7.
9. Use of the poly-3-thiopheneacetic acid modified PCN-224 composite material according to claim 8, wherein the poly-3-thiopheneacetic acid modified PCN-224 composite material is used for preparing photosensitizer in tumor photodynamic therapy.
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