CN113912872A - Polypyrrole nanoparticle for copper-induced oxidative polymerization and preparation method and application thereof - Google Patents
Polypyrrole nanoparticle for copper-induced oxidative polymerization and preparation method and application thereof Download PDFInfo
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- CN113912872A CN113912872A CN202111076774.9A CN202111076774A CN113912872A CN 113912872 A CN113912872 A CN 113912872A CN 202111076774 A CN202111076774 A CN 202111076774A CN 113912872 A CN113912872 A CN 113912872A
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/12—Powdering or granulating
- C08J3/14—Powdering or granulating by precipitation from solutions
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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
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/06—Polycondensates having nitrogen-containing heterocyclic rings in the main chain of the macromolecule
- C08G73/0605—Polycondensates containing five-membered rings, not condensed with other rings, with nitrogen atoms as the only ring hetero atoms
- C08G73/0611—Polycondensates containing five-membered rings, not condensed with other rings, with nitrogen atoms as the only ring hetero atoms with only one nitrogen atom in the ring, e.g. polypyrroles
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2379/00—Characterised by the use of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing nitrogen with or without oxygen, or carbon only, not provided for in groups C08J2361/00 - C08J2377/00
- C08J2379/04—Polycondensates having nitrogen-containing heterocyclic rings in the main chain; Polyhydrazides; Polyamide acids or similar polyimide precursors
Abstract
The invention belongs to the technical field of biological medicines, and particularly relates to a polypyrrole nanoparticle for copper-induced oxidative polymerization, and a preparation method and application thereof. The polypyrrole nanoparticles are prepared by inducing pyrrole monomers to be oxidized and polymerized by adopting a copper-containing oxidant, the preparation method is simple to operate, and the particle size of a material can be regulated and controlled by the addition amount of a stabilizer; the prepared polypyrrole nanoparticle material has a good photo-thermal effect, can also obviously improve a tumor microenvironment, and can achieve a synergistic effect after reaching a tumor part so as to achieve an effect of obviously killing tumor cells; the polypyrrole nano material has excellent biocompatibility and stability, can be absorbed by organisms, has high safety, and is very suitable for being used as a tumor medicament in clinical application.
Description
Technical Field
The invention belongs to the technical field of biological medicines. More particularly, relates to polypyrrole nanoparticles subjected to copper-induced oxidative polymerization, and a preparation method and application thereof.
Background
Photothermal therapy refers to a method of treating a disease by converting light energy into heat energy and using the converted heat energy. In recent years, due to the characteristics of strong targeting and wide adaptability of photothermal therapy, the research on the photothermal therapy has been widely focused. Compared with radiotherapy and surgery in traditional tumor treatment, the photothermal treatment has obviously reduced damage to normal tissues of human body.
Polypyrrole has good biocompatibility and excellent photothermal effect and photostability, and is widely used in the field of photothermal therapy. For example, chinese patent application CN108815524A discloses a drug-loaded phase-change material-coated polypyrrole photothermal therapeutic agent modified with hyaluronic acid, wherein polypyrrole of the photothermal therapeutic agent is induced to polymerize by using ferric chloride as an oxidant, and the polypyrrole exists in the final product and does not act, and the in vivo clearance pathway is unclear. On the other hand, the tumor microenvironment has the characteristics of hypoxia, high-concentration superoxide or glutathione overexpression and the like, the treatment effect is obviously limited, the tumor cannot be thoroughly eliminated by simple photothermal treatment, and the clinical anti-tumor effect is limited.
Disclosure of Invention
The invention aims to solve the technical problem of overcoming the defect and the defect of limited effect of the existing polypyrrole when used for photo-thermal treatment of cancers, and provides the copper-induced oxidative polymerization polypyrrole nanoparticles which are high in safety, can improve the tumor microenvironment, and can resist tumors in a synergistic manner by combining photo-thermal treatment.
The invention aims to provide a preparation method of the polypyrrole nanoparticles through copper-induced oxidative polymerization.
The invention also aims to provide the application of the polypyrrole nanoparticles subjected to copper-induced oxidative polymerization in preparing the tumor prevention and treatment medicines.
The above purpose of the invention is realized by the following technical scheme:
a preparation method of polypyrrole nanoparticles by copper-induced oxidative polymerization comprises the following steps:
s1, mixing the stabilizer, the oxidant and the pyrrole monomer to prepare a mixed solution, stirring and reacting at 4-30 ℃, centrifuging at 3000-8000 rpm for the first time, collecting supernatant at 10000-50000 rpm for the second time, and collecting precipitate to obtain polypyrrole nanoparticles;
s2, preparing the polypyrrole nanoparticles obtained in the step S1 into a dispersion liquid, adding polyethylene glycol, performing ultrasonic reaction completely, centrifuging for the third time, and performing precipitation post-treatment to obtain the polypyrrole nanoparticle dispersion liquid;
wherein the oxidant is selected from one or more of copper chloride, copper nitrate and copper oxide. Preferably, the oxidizing agent is selected from copper chloride.
Further, in step S1, the stabilizer is selected from one or more of polyvinyl alcohol, polyvinylpyrrolidone, polyethylene oxide, and sodium lauryl sulfate.
Further, in step S1, the amount of the stabilizer added is 0.1 to 10 mg/mL. The effect of regulating and controlling the particle size of the polypyrrole nanoparticles can be realized by adjusting the addition amount of the stabilizer in the reaction system.
Further, in step S1, the amount of the oxidizing agent added is 10 to 100 mg/mL.
Further, in step S1, the volume ratio of the pyrrole monomer to the total volume of the mixed solution is 1: (10-500).
Preferably, in step S1, the rotation speed of the stirring is 200 to 1500 rpm.
Preferably, in step S1, the stirring reaction time is 8 to 30 hours.
Preferably, in the step S1, the reaction temperature of the stirring reaction is 20 to 30 ℃.
Further, in step S2, the mass ratio of the polypyrrole nanoparticles to the polyethylene glycol is 1: (4-20).
Preferably, in step S2, the time of the ultrasonic reaction is 8 to 36 hours.
In addition, the invention also provides a polypyrrole nano-particle material prepared by the preparation method and used for copper-induced oxidative polymerization.
Further, the particle size of the polypyrrole nanoparticle material is 20-300 nm.
In addition, the invention also provides application of the polypyrrole nano-particle material subjected to copper-induced oxidative polymerization in preparation of a tumor prevention and treatment drug.
Further, the medicine is combined with photothermal therapy to prevent and treat tumors.
The polypyrrole nanoparticle material subjected to copper-induced oxidative polymerization provided by the invention creatively adopts a copper-containing oxidant to induce pyrrole monomer to undergo oxidative polymerization, the prepared polypyrrole nanoparticle material reserves copper elements in the oxidant, the obtained polypyrrole nanoparticle material has good photo-thermal properties, has high temperature rise under the laser stimulation of a near-infrared region I and a near-infrared region II, shows good photo-thermal effects, is burned and killed by the photo-thermal effects, and has high safety; in addition, under the condition of an anoxic tumor microenvironment, the prepared polypyrrole nanoparticle material can play a nanometer catalysis role, a large number of hydroxyl oxygen free radicals are generated while glutathione with an antioxidant effect is consumed, the catalysis efficiency is enhanced along with the rise of temperature, the disorder of the tumor microenvironment is promoted, the biodegradation of the nanoparticles is accelerated, and safe and effective anticancer treatment is realized. In addition, the polypyrrole provided by the invention has excellent biocompatibility and stability, can be absorbed by the body, and is high in safety.
The invention has the following beneficial effects:
the invention provides a polypyrrole nanoparticle material for copper-induced oxidative polymerization, which adopts a copper-containing oxidant to induce pyrrole monomer oxidative polymerization, has simple preparation method operation, and can regulate and control the particle size of the material through the addition of a stabilizer; the prepared polypyrrole nanoparticle material has a good photo-thermal effect, can also obviously improve a tumor microenvironment, and can achieve a synergistic effect after reaching a tumor part so as to achieve an effect of obviously killing tumor cells; the polypyrrole nano material has excellent biocompatibility and stability, can be absorbed by organisms, has high safety, and is very suitable for being used as a tumor medicament in clinical application.
Drawings
Fig. 1 is an electron microscope scanning image of polypyrrole nanoparticles with copper induced oxidative polymerization modified by polyethylene glycol obtained in example 3 of the present invention, wherein fig. 1A: 10mg of polyvinyl alcohol was added; FIG. 1B: 30mg of polyvinyl alcohol were added; FIG. 1C: 50mg of polyvinyl alcohol was added; FIG. 1D: 100mg of polyvinyl alcohol were added.
Fig. 2 is a particle size distribution diagram of polypyrrole nanoparticles with copper induced oxidative polymerization modified by polyethylene glycol obtained in example 3 of the present invention.
FIG. 3 is an X-ray photoelectron spectrum of polypyrrole nanoparticles oxidized and polymerized by copper induced by polyethylene glycol modified with 30mg of polyvinyl alcohol in example 3 of the present invention.
FIG. 4 is an X-ray diffraction pattern of polypyrrole nanoparticles obtained by copper-induced oxidative polymerization modified by polyethylene glycol with 30mg of polyvinyl alcohol in example 3 of the present invention.
Fig. 5 is an electron microscope scanning image and a particle size distribution diagram of polypyrrole nanoparticles subjected to copper-induced oxidative polymerization and modified by polyethylene glycol obtained in example 1 in test example 1 of the present invention.
Fig. 6 is a statistical chart of the optical absorption and photothermal performance research on polypyrrole nanoparticles subjected to copper-induced oxidative polymerization and modified by polyethylene glycol obtained in example 1 in experimental example 2 of the present invention, where fig. 6A: ultraviolet visible absorption spectrum; FIG. 6B: excitation by 808nm laser; FIG. 6C: laser excitation at 1064 nm.
Fig. 7 is a statistical chart of the catalytic performance results of polypyrrole nanoparticles subjected to copper-induced oxidative polymerization modified by polyethylene glycol obtained in example 1 in test example 3 of the present invention, where fig. 7A: oxygen production capacity test results; FIG. 7B: hydroxyl oxygen radical generating capability test results; FIG. 7C: results of glutathione consumption capacity test.
Fig. 8 is a statistical chart of cytotoxicity test results of polypyrrole nanoparticles subjected to copper-induced oxidative polymerization modified by polyethylene glycol obtained in example 1 in test example 3 of the present invention, in which fig. 8A: no 1064nm laser illumination is performed; FIG. 8B: and (3) irradiating 1064nm laser.
Detailed Description
The invention is further described with reference to the drawings and the following detailed description, which are not intended to limit the invention in any way. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated.
Unless otherwise indicated, reagents and materials used in the following examples are commercially available.
Example 1 polypyrrole nanoparticles with copper induced oxidative polymerization modified by polyethylene glycol
The preparation method of the polypyrrole nanoparticles with copper induced oxidative polymerization modified by polyethylene glycol comprises the following steps:
s1, adding 10mL of deionized water into a 50mL single-neck round-bottom flask, adding 30mg of polyvinyl alcohol (PVA), carrying out mild stirring, condensing and refluxing for 1 hour under a heating environment at 90 ℃, and then naturally cooling to room temperature; under the stirring condition of the rotating speed of 600-1500 rpm (magnetic stirring), dropwise adding 10mL of copper chloride solution (containing 1g of copper chloride), and continuously stirring for 1 hour; then, dropwise adding 200 mu L of pyrrole monomer (99 percent, avastin), stirring at 600-1500 rpm (magnetic stirring), and reacting for 24 hours; centrifuging the obtained reaction solution by a low-temperature ultracentrifuge at 5000rpm/min for 10min, removing large-particle nanoparticles, collecting supernatant, centrifuging at 20000rpm/min for 20min, and collecting precipitate to obtain polypyrrole nanoparticles;
s2, under the condition of constant-temperature ice-water bath ultrasound, dropwise adding 1mL of distearoyl phosphatidyl ethanolamine polyethylene glycol (DSPE-PEG) solution (5mg/mL, the solvent is acetone: ethanol ═ 2:3) into 1mL of polypyrrole nanoparticle dispersion liquid (1mg/mL) obtained in the step S1, continuing ultrasound for 30 minutes, and magnetically stirring at 600-1500 rpm for overnight reaction; centrifuging the reaction solution at 20000rpm for 20min, and washing the precipitate with ultrapure water twice to obtain the final product.
Example 2 polypyrrole nanoparticles with copper induced oxidative polymerization modified by polyethylene glycol
The preparation method of the polypyrrole nanoparticles with copper induced oxidative polymerization modified by polyethylene glycol comprises the following steps:
s1, adding 10mL of deionized water into a 50mL single-neck round-bottom flask, adding 50mg of polyvinyl alcohol (PVA), carrying out mild stirring, condensing and refluxing for 1 hour under a heating environment at 90 ℃, and then naturally cooling to room temperature; under the stirring condition of the rotating speed of 600-1500 rpm (magnetic stirring), dropwise adding 10mL of copper oxide solution (containing 1g of copper oxide), and continuously stirring for 1 hour; then, dropwise adding 200 mu L of pyrrole monomer (99 percent, avastin), stirring at 600-1500 rpm (magnetic stirring), and reacting for 20 hours; centrifuging the obtained reaction solution by a low-temperature ultracentrifuge at 5000rpm/min for 10min, removing large-particle nanoparticles, collecting supernatant, centrifuging at 20000rpm/min for 20min, and collecting precipitate to obtain polypyrrole nanoparticles;
s2, under the condition of constant-temperature ice-water bath ultrasound, dropwise adding 1mL of distearoyl phosphatidyl ethanolamine polyethylene glycol (DSPE-PEG) solution (3mg/mL, the solvent is acetone: ethanol ═ 2:3) into 1mL of polypyrrole nanoparticle dispersion liquid (1mg/mL) obtained in the step S1, continuing ultrasound for 30 minutes, and magnetically stirring at 600-1500 rpm for overnight reaction; centrifuging the reaction solution at 20000rpm for 20min, and washing the precipitate with ultrapure water twice to obtain the final product.
Example 3 polypyrrole nanoparticles with copper induced oxidative polymerization modified by polyethylene glycol
The preparation method of the polypyrrole nanoparticles with copper induced oxidative polymerization modified by polyethylene glycol refers to example 1, except that 10mg, 30mg, 50mg and 100mg of polyvinyl alcohol are added in step S1, and the rest parameters and operation refer to example 1.
And (3) performing electron microscope scanning observation and particle size distribution analysis on the polypyrrole nanoparticles subjected to copper-induced oxidative polymerization modified by polyethylene glycol, and obtaining results shown in the figures 1-2. It can be seen from the figure that, with the change of the addition amount of the polyvinyl alcohol from high to low, the electron microscope particle size and the hydrodynamic particle size of the polypyrrole nanoparticle modified by the polyethylene glycol and subjected to copper-induced oxidative polymerization become larger gradually, and the nanoparticle prepared under the condition of 30mg of polyvinyl alcohol addition amount has the best dispersibility and the best uniformity. The size and the dispersibility of the nanoparticles can be regulated and controlled by controlling the amount of the stabilizer polyvinyl alcohol in the reaction system.
And (3) carrying out X-ray photoelectron spectroscopy and X-ray diffraction pattern analysis on the nanoparticles prepared by adding 30mg of polyvinyl alcohol, and obtaining results shown in figures 3-4. As can be seen from FIG. 3, the prepared nanoparticles have Cu, C, N, O and Cl elements, which indicates that the polypyrrole nanoparticles prepared by modifying copper with polyethylene glycol and inducing oxidative polymerization are successfully prepared; as can be seen from FIG. 4, the polypyrrole characteristic absorption peak of the prepared nanoparticle exists, which indicates that the polypyrrole nanoparticle of the invention, which is modified by polyethylene glycol and subjected to copper-induced oxidative polymerization, is successfully prepared.
Test example 1 test of physical and chemical Properties
Physical and chemical performance tests are carried out by taking the polypyrrole nanoparticles subjected to copper-induced oxidative polymerization and modified by polyethylene glycol obtained in example 1 as an example, and the effects of the other examples are similar to those of example 1.
The polypyrrole nanoparticles obtained by copper-induced oxidative polymerization modified by polyethylene glycol in example 1 were observed by scanning electron microscopy and analyzed for particle size distribution, and the results are shown in fig. 5.
As can be seen from FIG. 5, the polypyrrole nanoparticles obtained by copper-induced oxidative polymerization modified by polyethylene glycol have uniform size and good dispersibility, and the hydrodynamic particle size is about 99.67 nm.
Test example 2 optical Property test
The polypyrrole nanoparticles obtained in example 1 and subjected to copper-induced oxidative polymerization are taken as an example for optical performance test, and the effects of the other examples are similar to those of example 1.
Under the laser conditions of 808nm and 1064nm wavelengths, the optical absorption and photo-thermal properties of polypyrrole nanoparticles with copper induced oxidative polymerization modified by polyethylene glycol at different concentrations were evaluated, and the results are shown in fig. 6.
As can be seen from fig. 6A, the polypyrrole nanoparticles oxidized and polymerized by copper induced by polyethylene glycol modification have strong optical absorption in the near-infrared I and II regions, and have concentration dependence; as can be seen from fig. 6B and 6C, the polypyrrole nanoparticles with copper-induced oxidative polymerization modified by polyethylene glycol have higher temperature rise under the excitation of 808nm and 1064nm lasers, and have excellent photo-thermal properties.
Therefore, the polypyrrole nanoparticles modified by polyethylene glycol and subjected to copper-induced oxidative polymerization have the temperature required by photo-thermal treatment of cauterized tumors, and the laser response capability of the near-infrared region II can greatly increase the cure rate of deep tumors.
Test example 3 test of catalytic Performance
The polypyrrole nanoparticles obtained in example 1 and subjected to copper-induced oxidative polymerization are taken as an example for carrying out a catalytic performance test, and the effects of the other examples are similar to those of example 1.
The oxygen production capacity, hydroxyl oxygen radical production capacity and glutathione consumption capacity of the polypyrrole nanoparticles subjected to copper-induced oxidative polymerization modified by polyethylene glycol were respectively tested, and the results are shown in fig. 7.
The oxygen production capacity test method comprises the following steps: different concentrations of polypyrrole nanoparticles (0, 10, 20, 40 μ g/mL) modified with polyethylene glycol and subjected to copper-induced oxidative polymerization were dispersed in phosphate buffer (pH 7.4) and once H was added by syringe2O2(10mM), the oxygen concentration of the solution was measured at various time points using a JPSJ-605F portable dissolved oxygen meter, and the results are shown in FIG. 7A.
The hydroxyl oxygen radical generating capacity test method comprises the following steps: dispersing polypyrrole nano particles (0, 10, 20 and 40 mu g/mL) with different concentrations of polyethylene glycol modified copper-induced oxidative polymerization in a phosphate buffer solution (pH 7.4), then adding a 10 mu g/mL methylene blue indicator, and finally adding H2O2(10mM), and the UV absorption of the solution was measured by UV-visible spectrometer at different time points, and the results are shown in FIG. 7B.
The method for testing the glutathione consumption capacity comprises the following steps: polypyrrole nanoparticles (0, 0.625, 1.25, 2.5, 5 μ g/mL) with different concentrations of polyethylene glycol-modified copper-induced oxidative polymerization were dispersed in phosphate buffer (pH 7.4), then 0.1mM GSH was added, and finally the consumption of GSH was detected using a 5,5' -dithiobis (2-nitrobenzoic acid) probe, the results of which are shown in fig. 7C.
As can be seen from fig. 7A, the polypyrrole nanoparticles with copper-induced oxidative polymerization modified by polyethylene glycol have strong oxygen generation capability and concentration dependence, and can alleviate tumor hypoxia; as can be seen from fig. 7B, the polypyrrole nanoparticle with copper-induced oxidative polymerization modified by polyethylene glycol has a significant hydroxyl radical generating ability, has concentration dependency, and can aggravate a tumor oxidation microenvironment. As can be seen from fig. 7C, the polypyrrole nanoparticles with copper-induced oxidative polymerization modified by polyethylene glycol have an obvious glutathione removing ability, and can reduce the tumor oxidation resistance.
Therefore, the polypyrrole nanoparticle modified by polyethylene glycol and subjected to copper-induced oxidative polymerization provided by the invention has the capabilities of remolding a tumor microenvironment and powerful nano catalytic treatment, and has the capabilities of killing tumors and preventing tumor recurrence and metastasis.
Test example 4 cytotoxicity test
The polyethylene glycol modified copper-induced oxidative polymerization polypyrrole nanoparticles obtained in example 1 are taken as an example to respectively perform cytotoxicity tests on normal cells and tumor cells, and the effects of the other examples are similar to those of example 1.
The test method comprises the following steps: respectively mixing mouse breast cancer cell 4T1, human glioma cell U87, human umbilical vein endothelial cell HUVEc and mouse microglial cell BV2At a rate of 8X 10 per hole3The density of each cell was inoculated in a 96-well plate and cultured for 12 hours; after washing once with PBS, cells were incubated with gradient concentrations (0, 2.5, 5, 10, 20, 40, 80, 120 μ g/mL) of peg-modified copper-induced oxidative polymerization polypyrrole nanoparticles for 24 hours; after washing with PBS, Cell Counting Kit-8(CCK-8) was incubated for 2 hours, absorbance was measured at 450nm wavelength, and standard Cell viability assays were performed to determine relative Cell viability, the results of which are shown in FIG. 8A.
Mouse breast cancer cells 4T1 cells at 8X 10 per well3The density of each cell was inoculated in a 96-well plate and cultured for 12 hours; after washing once with PBS, the cells were incubated with gradient concentrations (0, 2.5, 5, 10, 20, 40. mu.g/mL) of PEG-modified Cu-induced oxidative polymerization polypyrrole nanoparticles for 4 hours, followed by different powers (0.5, 1.0, 1.5W/cm)2) 1064nm laser irradiation for 5 minutes; the incubation was continued for 20 hours, washed with PBS, incubated for 2 hours using Cell Counting Kit-8(CCK-8), absorbance was measured at a wavelength of 450nm, and standard Cell viability assay was performed to determine relative cellsViability, results are shown in figure 8B.
As can be seen from fig. 8A, under the condition of no laser light, the polypyrrole nanoparticles modified by different concentrations of polyethylene glycol and subjected to copper-induced oxidative polymerization have almost no toxicity to normal cells and tumor cells; however, under the condition of 1064nm laser light, the concentration and power dependence of the toxicity of the polypyrrole nanoparticles subjected to copper-induced oxidative polymerization and modified by polyethylene glycol on tumor cells is presented.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (10)
1. A preparation method of polypyrrole nanoparticles by copper-induced oxidative polymerization is characterized by comprising the following steps:
s1, mixing the stabilizer, the oxidant and the pyrrole monomer to prepare a mixed solution, stirring and reacting at 4-30 ℃, centrifuging at 3000-8000 rpm for the first time, collecting supernatant at 10000-50000 rpm for the second time, and collecting precipitate to obtain polypyrrole nanoparticles;
s2, preparing the polypyrrole nanoparticles obtained in the step S1 into a dispersion liquid, adding polyethylene glycol, performing ultrasonic reaction completely, centrifuging for the third time, and performing precipitation post-treatment to obtain the polypyrrole nanoparticle dispersion liquid;
wherein the oxidant is selected from one or more of copper chloride, copper nitrate and copper oxide.
2. The method according to claim 1, wherein in step S1, the stabilizer is one or more selected from polyvinyl alcohol, polyvinylpyrrolidone, polyethylene oxide, and sodium lauryl sulfate.
3. The method according to claim 1, wherein the stabilizer is added in an amount of 0.1 to 10mg/mL in step S1.
4. The method according to claim 1, wherein in step S1, the amount of the oxidizing agent added is 10 to 100 mg/mL.
5. The method according to claim 1, wherein in step S1, the volume ratio of the pyrrole monomer to the total volume of the mixed solution is 1: (10-500).
6. The preparation method according to claim 1, wherein in step S2, the mass ratio of the polypyrrole nanoparticles to the polyethylene glycol is 1: (4-20).
7. A polypyrrole nanoparticle material for copper-induced oxidative polymerization prepared by the preparation method of any one of claims 1 to 6.
8. The polypyrrole nanoparticle material for copper-induced oxidative polymerization according to claim 7, wherein the particle size of the polypyrrole nanoparticle material is 20-300 nm.
9. The use of the polypyrrole nanoparticle material of claim 7 or 8, which undergoes oxidative polymerization induced by copper, in the preparation of a drug for preventing and treating tumors.
10. The use of claim 9, wherein the medicament is for the prevention or treatment of tumors in combination with photothermal therapy.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4604427A (en) * | 1984-12-24 | 1986-08-05 | W. R. Grace & Co. | Method of forming electrically conductive polymer blends |
| CN1101161A (en) * | 1993-09-30 | 1995-04-05 | 中国科学院化学研究所 | conductive polymer composite film and preparation method |
| CN105854034A (en) * | 2016-06-23 | 2016-08-17 | 吉林大学 | Metal ion copper-doped polyaminopyrrole composite nano-particle diagnosis and treatment reagent as well as preparation method and application thereof |
| CN108853059A (en) * | 2018-08-03 | 2018-11-23 | 上海理工大学 | A kind of polypyrrole-polyvinylpyrrolidone nano particle and its preparation method and application |
| CN111803466A (en) * | 2020-04-17 | 2020-10-23 | 中山大学 | Preparation method and application of polypyrrole nanoparticles with controllable particle size |
-
2021
- 2021-09-14 CN CN202111076774.9A patent/CN113912872A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4604427A (en) * | 1984-12-24 | 1986-08-05 | W. R. Grace & Co. | Method of forming electrically conductive polymer blends |
| CN1101161A (en) * | 1993-09-30 | 1995-04-05 | 中国科学院化学研究所 | conductive polymer composite film and preparation method |
| CN105854034A (en) * | 2016-06-23 | 2016-08-17 | 吉林大学 | Metal ion copper-doped polyaminopyrrole composite nano-particle diagnosis and treatment reagent as well as preparation method and application thereof |
| CN108853059A (en) * | 2018-08-03 | 2018-11-23 | 上海理工大学 | A kind of polypyrrole-polyvinylpyrrolidone nano particle and its preparation method and application |
| CN111803466A (en) * | 2020-04-17 | 2020-10-23 | 中山大学 | Preparation method and application of polypyrrole nanoparticles with controllable particle size |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115998866A (en) * | 2022-12-30 | 2023-04-25 | 中山大学·深圳 | Copper-induced polypyrrole/black phosphorus heterojunction material and preparation method and application thereof |
| CN115998866B (en) * | 2022-12-30 | 2023-12-15 | 中山大学·深圳 | Copper-induced polypyrrole/black phosphorus heterojunction material and preparation method and application thereof |
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