CN110917349A - Bowl-shaped ISP (internet service provider) composite functional nano particle as well as preparation method and application thereof - Google Patents
Bowl-shaped ISP (internet service provider) composite functional nano particle as well as preparation method and application thereof Download PDFInfo
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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
- A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5115—Inorganic compounds
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
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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
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Abstract
The invention discloses bowl-shaped ISP (internet service provider) composite functional nanoparticles as well as a preparation method and application thereof, wherein a block polymer is self-assembled and then loaded with Fe3O4Particles and photosensitizer ZnPc; the block polymer is bowl-shaped polyethylene glycol block polystyrene (PEG-b-PS). The bowl-shaped ISP functional composite nano particle prepared by the invention has a magnetic targeting function and can improve the enrichment of ZnPc in tumor tissue parts, the novel bowl-shaped ISP functional composite nano particle can be magnetically targeted to the tumor tissue parts, the activity of a photosensitizer is improved by catalyzing oxygen production, and the purpose of realizingHigh-efficiency treatment of PDT. The preparation method is simple and convenient, the raw materials are wide in source and high in bioavailability, and the prepared nanoparticles are used as a photosensitizer and a carrier to be applied to preparation of photodynamic medicaments.
Description
Technical Field
The invention belongs to the technical field of nano systems capable of improving photodynamic activity, and particularly relates to bowl-shaped ISP (internet service provider) composite functional nanoparticles and a preparation method and application thereof, in particular to magnetic targeted functional composite nanoparticles and application thereof in photosensitive treatment of tumors.
Background
Photodynamic therapy (PDT) is a novel method for treating tumors. The photosensitizer enters a human body through intravenous injection, then the photosensitizer positioned at a tumor part is excited by light with specific wavelength to react with surrounding oxygen to generate active oxygen, and biological macromolecules in tumor cells are damaged through oxidation, so that the tumor cells are killed, and the effect of tumor treatment is achieved. PDT has received much attention because of its low toxic side effects, drug resistance and reusable characteristics. Zinc phthalocyanine (ZnPc for short) has high biological safety (low dark toxicity) and photosensitive antitumor activity as a metal complex photosensitizer with application prospect.
The structure formed by self-assembling the block polymer with Polyethylene glycol (PEG) at one end through solution has high drug-loading application value, and the PEG has good biocompatibility and can prolong the circulation time of the loaded drug in blood. The structure has more than two characteristics, and provides more possibilities for loading various medicines. Currently, nanotechnology is widely used in drug delivery and functionalization systems, where magnetic Fe is present3O4Nanoparticles are of great interest in the field of tumor therapy because of their excellent magnetic targeting. In the photodynamic therapy, the medicament is easy to remove in blood circulation, and the medicament has poor targeting property, so that toxic and side effects on healthy tissues are caused, and the development of the photodynamic therapy is greatly limited. In addition, the phthalocyanine photosensitizer consumes oxygen by illumination, and the oxygen is not supplied enough, so that the activity of the photosensitizer is limited, and the antitumor effect of the photosensitizer in cells is reduced.
Disclosure of Invention
The purpose of the invention is as follows: aiming at the problems in the prior art, the invention provides a novel bowl-shaped ISP composite functional nanoparticle which can be magnetically targeted to a tumor tissue part, and can improve the activity of a photosensitizer by catalyzing oxygen generation to realize high-efficiency treatment of PDT.
The invention also provides a preparation method of the ISP composite functional nano particle and application of the ISP composite functional nano particle in preparation of photosensitive drugs.
The technical scheme is as follows: in order to achieve the above purpose, the bowl-shaped ISP composite functional nanoparticle according to the present invention is characterized in that Fe is loaded after the block polymer is self-assembled into a bowl-shaped structure3O4Particles and photosensitizer ZnPc; the block polymer is polyethylene glycol block polystyrene, which is referred to as PEG-b-PS for short.
Wherein the bowl-shaped ISP composite functional nano particle is of a bowl-shaped structure and Fe3O4The nano particles are loaded in the groove of the bowl-shaped structure to form a functional nano carrier with magnetic targeting, and then the ISP functional composite nano particles are obtained by loading a photosensitizer ZnPc.
Further, the bowl-shaped ISP composite functional nano particle is an organic-inorganic composite nano particle suitable for intravenous injection.
The preparation method of the bowl-shaped ISP functional composite nano particle comprises the following steps:
(1) preparing a bowl-shaped structure PEG-b-PS self-assembly structure: dissolving PEG-OH in tetrahydrofuran uniformly, and dissolving in N2Protecting, adding 2-bromoisobutyryl bromide into ice-water bath at 0 deg.C for reaction, vacuum filtering the product, and adding NaHCO into the supernatant3Extracting the solution, and drying in vacuum to obtain a PEG-Br macromolecular initiator; dissolving a PEG-Br macromolecular initiator in anisole to dissolve, adding styrene, CuCl and PMDETA to react, purifying and separating a product, carrying out reduced pressure distillation and concentration on the obtained solution, then settling in a methanol solution, carrying out suction filtration on the precipitate, and carrying out vacuum drying to obtain a polyethylene glycol block polystyrene polymer, namely PEG-b-PS; dissolving PEG-b-PS in a mixed solution of 1, 4-dioxane and tetrahydrofuran, and injecting double distilled water to obtain PEG-b-PS with a bowl-shaped structure;
(2) superparamagnetic Fe3O4And (3) synthesis of nanoparticles: mixing Fe (acac)3Dissolving in triethylene glycol, and synthesizing superparamagnetic Fe by thermal decomposition method3O4A nanoparticle solution;
(3) of bowl-shaped ISP functional composite nanoparticlesPreparation: fe modified by triethylene glycol3O4Mixing the nanoparticle solution with the PEG-b-PS solution with a bowl-shaped structure, and making Fe by the similar intermiscibility of the structures between triethylene glycol and PEG3O4Loading nano particles into PEG-b-PS with a bowl-shaped structure, and obtaining the loaded Fe by centrifugal separation after ultrasonic treatment3O4And adding a ZnPc solution into the nano particles with the bowl-shaped PEG-b-PS structure of the nano particles, mixing, and performing centrifugal separation after ultrasonic treatment to obtain the bowl-shaped ISP functional composite nano particles.
Wherein, the PEG-Br in the step (1) is dissolved in anisole, and the styrene, CuCl and PMDETA are added for reaction, and the reaction is carried out overnight at 80-100 ℃ under the anhydrous and oxygen-free conditions of the mixture; the preferred temperature is 90 ℃.
Wherein, the feeding conditions of the PEG-Br and the styrene in the step (1) are argon protection and liquid nitrogen atmosphere.
Specifically, the feeding period of the PEG-Br and the styrene in the step (1) is in an argon atmosphere, and the low-temperature state of the raw materials is kept by placing a reaction container in an ice-water bath at 0 ℃.
Wherein, the superparamagnetic Fe is synthesized by the thermal decomposition method in the step (2)3O4The nano particle solution is Fe (acac)3After dissolving uniformly in triethylene glycol, N2Under protection, the temperature is increased to 200 ℃, 250 ℃ and 280 ℃ in a gradient way, and the superparamagnetic Fe is obtained after reflux reaction for 0.5 to 1 hour at 280 DEG C3O4A nanoparticle solution.
Preferably, the gradient temperature rise in the step (2) is maintained at 200 ℃ and 250 ℃ for 5-10min respectively.
Further, the bowl-shaped structures PEG-b-PS and Fe in the step (3)3O4ZnPc in a mass ratio of 2-3:1.5-2.5:0.5-1.5, and further, the PEG-b-PS and Fe in the step (3)3O4And the mass ratio of ZnPc is 2:2: 1.
The bowl-shaped ISP functional composite nano particle is applied to preparation of a photodynamic medicament.
The bowl-shaped ISP functional composite nano particle is used as a photosensitizer and a carrier in the preparation of a photodynamic medicament.
The invention synthesizes PEG-b-PS by ATRP method, obtains bowl-shaped structure by self-assembly of solution, and synthesizes superparamagnetism Fe by thermal decomposition method3O4Nano particles, ZnPc is synthesized by DBU catalysis method, and superparamagnetic Fe is added into PEG-b-PS solution with bowl structure3O4Centrifuging the nanoparticle solution to remove unadsorbed Fe3O4Adding a photosensitizer ZnPc, centrifuging to remove the unadsorbed ZnPc, and centrifuging and washing the product to obtain the bowl-shaped ISP functional composite nano particle.
Preferably, the PEG-b-PS is dissolved uniformly in tetrahydrofuran by PEG-OH and then is dissolved in N2Protection and ice water bath, adding 2-bromine isobutyryl bromide for reaction, filtering the product, and using NaHCO as supernatant3Extracting the solution, and drying in vacuum to obtain the PEG-Br macromolecular initiator. Dissolving PEG-Br macroinitiator in anisole, dissolving, transferring the solution into a Schlenk bottle, adding styrene, CuCl and PMDETA, reacting the mixture at 90 ℃ under anhydrous and anaerobic conditions overnight, removing a complex containing cuprous ions from the product by a neutral alumina chromatographic column, carrying out reduced pressure distillation and concentration on the obtained solution, settling the obtained solution in a methanol solution, carrying out suction filtration on the precipitate, and carrying out vacuum drying to obtain a PEG-b-PS polymer, wherein the polymer is assembled into a bowl-shaped structure in a mixed solvent of tetrahydrofuran, 1, 4-dioxane and water, and the shape of the polymer is as shown in figure 3 and the bowl-shaped structure.
The bowl-shaped ISP functional composite nano particle prepared by the invention is applied to the preparation of photosensitive drugs. Aiming at the problem of insufficient targeting of the photosensitizer at a tumor part, the invention takes PEG-b-PS with a bowl-shaped structure as a carrier and Fe3O4The magnetic targeting ability of the nanoparticles, the bowl-shaped ISP functional composite nanoparticles are constructed, and efficient tumor targeted PDT treatment is realized. The bowl-shaped ISP functional composite nano particle has good biocompatibility and basically no toxicity in cells. Has excellent capacity of targeting tumor tissue magnetically, can improve the uptake of the cell to the medicine and enhance the PDT effect of the photosensitizer.
The mechanism is as follows: one end of the PEG-b-PS self-assembly structure is PEG, so the PEG-b-PS self-assembly structure has good biocompatibility, and the polymer PEG-b-PS has twoAffinity, which is beneficial to the loading of the medicine; and Fe loaded in the bowl-shaped groove3O4The nano-particles add a magnetic targeting function, and ZnPc is adsorbed on the surface of a PEG-b-PS structure with a bowl-shaped structure, so that the whole composite nano-particle has photodynamic therapy activity. Due to the microenvironment of the tumor tissue and the relatively high concentration of H in the cells2O2，H2O2Quilt Fe3O4The catalysis generates oxygen, and the oxygen content in the tumor cells is improved, thereby improving the activity of ZnPc. After the composite nano particles are injected into a living body, the composite nano particles are targeted to a tumor part through an external magnetic field, and the PDT effect is improved.
The raw materials used in the present invention are all commercially available.
Has the advantages that: compared with the prior art, the invention has the following advantages:
(1) the PEG-b-PS nano structure with the bowl-shaped structure has the advantages of simple assembly mode, good dispersibility and uniform size.
(2) The bowl-shaped ISP functional composite nano particle prepared by the invention has a magnetic targeting function and can improve the enrichment of ZnPc in tumor tissue parts.
(3) By O2The detection of the probe shows that the bowl-shaped ISP functional composite nano particle prepared by the invention has good H2O2The catalytic ability can relieve the hypoxic condition of tumor tissues.
(4) In-vivo anti-tumor experiments show that compared with ZnPc, the bowl-shaped ISP functional composite nano particle prepared by the invention has better tumor growth inhibition capability, and the effect is more obvious after a magnetic field is applied.
(5) The preparation method is simple and convenient, the raw materials are wide in source and high in bioavailability, and the prepared nanoparticles are used as a photosensitizer carrier and applied to preparation of photodynamic medicaments.
Drawings
FIG. 1 is a schematic structural diagram of a bowl-shaped ISP functional composite nanoparticle of the present invention;
FIG. 2 is a schematic diagram of the synthesis of a PEG-b-PS block polymer;
FIG. 3 is a transmission electron microscope image of the assembly of PEG-b-PS block polymers at the position of a bowl structure;
FIG. 4 is Fe3O4Transmission electron microscopy images of;
FIG. 5 is a schematic diagram of the synthesis of ZnPc;
FIG. 6 shows water, Fe3O4Zeta potential diagram of the bowl-shaped PEG-b-PS and bowl-shaped ISP composite functional nano particle;
FIG. 7 is a graph of the in vitro active oxygen yield of ZnPc, bowl-shaped ISP composite functional nanoparticles and their applied magnetic field;
FIG. 8 is a schematic view showing the phototoxicity of tumor cells after the ZnPc, bowl-shaped ISP functional composite nanoparticles and the external magnetic field are tested by the MTT method;
FIG. 9 is a schematic diagram showing the comparative ability of ZnPc, bowl-shaped ISP composite functional nanoparticles and their ability to inhibit tumor growth after being added with external magnetic field for targeting in a mouse transplanted tumor model animal body.
FIG. 10 is a nuclear magnetic image of bowl-shaped ISP complex functional nanoparticles in a mouse transplanted tumor model animal body under a magnetic field and a non-magnetic field for 24 h.
Detailed Description
The invention is further illustrated by the following figures and examples.
Example 1
PEG-b-PS block polymer is synthesized as shown in FIG. 2 by dissolving 3000 molecular weight poly (ethylene glycol) monomethyl ether (6.00g, 2.00mmol) in 20mL tetrahydrofuran, adding triethylamine (1.04mL, 7.5mmol), reacting the mixture at 0 deg.C in ice water bath and under nitrogen protection by dropwise adding 2-bromoisobutyryl bromide (620 μ L, 5.00mmol) for 24 hours, filtering to obtain white precipitate, vacuum drying to obtain PEG-Br-PEG-Br in 1.5mL anisole, adding CuCl (45mg, 0.45mmol) and PMDETA (α -bromosobutyrate, N, N, N' -Pentamethydiethylenetetramine, 66 μ L, 0.32mmol) under anhydrous condition and oxygen-free condition, reacting at 90 deg.C for 12 hours, placing in argon atmosphere during feeding, distilling in a distillation column at 0 deg.C to obtain 1mL tetrahydrofuran solution, concentrating the obtained by distilling the mixture of PEG-b-PS block polymer at 0.C, adding water solution and methanol to obtain a mixture, dissolving the precipitate in methanol solution at a ratio of 1mL tetrahydrofuran, dissolving the mixture of 1-1 mL tetrahydrofuran, concentrating the mixture at a distillation rate to obtain a mixture of tetrahydrofuran solution, and concentrating the mixture of the solution at a concentration of the solution of the mixture of aluminum oxide, wherein the solution of the mixture of the solution to obtain a solvent, and the solution, and the mixture of the solution, and the mixture of.
Example 2
Superparamagnetic Fe3O4Preparing nano particles: 1.42g Fe (acac)3After dissolving uniformly in 50mL of triethylene glycol, N2Under protection, the temperature is increased from room temperature to 200 ℃, then to 250 ℃ and finally to 280 ℃ in a gradient way, each stage is kept stable for 10min, and the reaction is carried out for 0.5h at 280 ℃ to obtain superparamagnetic Fe3O4Nanoparticle triethylene glycol solution. Prepared Fe3O4An electron micrograph of the nanoparticles is shown in FIG. 4.
Example 3
ZnPc synthesis: the synthesis of the side chain tetrasubstituted benzoic acid sodium salt phthalocyanine derivative was performed according to the procedure shown in fig. 5. Parahydroxybenzoic acid (500mg, 3.62mmol) and 4-nitrophthalonitrile (658mg, 3.8mmol) were dissolved in a mixed solvent of N, N-dimethylformamide (8mL) and potassium carbonate (561.2mg, 4.06mmol), and N2Under the protection condition, reacting to generate a compound 1; compound 1(500mg,1.89mmol) was reacted with zinc acetate (217mg,1.18mmol) catalyzed by DBU (0.38mL,2.82mmol) in n-pentanol (8mL) at 140 ℃ for 12h to give compound 2; compound 2(200mg, 0.18mmol) was reacted with sodium hydroxide (16mg, 0.4mmol) in ethanol (10mL) for 24h to finally yield the side chain tetrasubstituted benzoic acid sodium salt phthalocyanine derivative (ZnPc).
Example 4
Preparation of bowl-shaped ISP (internet service provider) composite functional nanoparticles: dialyzed 4mg/mL bowl-shaped PEG-b-PS solution obtained in example 1, with 6mg/mL Fe3O4The nano particle triethylene glycol solution is prepared according to PEG-b-PS and Fe3O4Mixing at a mass ratio of 2:2, centrifuging at 9600r/min for 5-10min to remove unloaded Fe3O4Nanoparticles of Fe except the grooves by ultrasonic removal3O4Nanoparticles. Diluting the prepared nanoparticle solution with distilled water until the concentration of the PEG-b-PS with the bowl-shaped structure is 1mg/mL, preparing 1mg/mL aqueous solution with the ZnPc prepared in the embodiment 3, mixing the aqueous solution and the ZnPc according to the mass ratio of 2:1 of the PEG-b-PS with the bowl-shaped structure and the ZnPc, and centrifuging at 9600r/min for 10min to remove the unloaded ZnPc to obtain the bowl-shaped ISP composite functional nanoparticles, wherein the shape of the bowl-shaped ISP composite functional nanoparticles is shown in figure 1.
Example 5
Zeta potential change determination of Fe3O4Nanoparticles and ZnPc loading case. The solution of PEG-b-PS with bowl structure obtained in example 1 and Fe obtained in example 23O4The nano-particle triethylene glycol solution, ZnPc obtained in example 3 and bowl-shaped ISP composite functional nano-particle obtained in example 4 are prepared according to the following steps of bowl-shaped structure PEG-b-PS: fe3O4Nanoparticle: ZnPc with a mass ratio of 100:20:7 was formulated into 2mL aqueous solution, in which the concentration of ZnPc was 2.8mg/mL, and its zeta potential value was tested. As shown in FIG. 6, PEG-b-PS and Fe can be obtained by the zeta potential value3O4The electrical property of the nano particles and ZnPc, and Fe can be obtained according to the fact that the zeta potential value of the bowl-shaped ISP composite functional nano particle solution is basically equal to the sum of the three potential values3O4The nanoparticles and ZnPc were successfully loaded on the bowl-shaped structure PEG-b-PS.
Example 6
ZnPc, bowl-shaped ISP composite functional nano particle and in-vitro oxygen detection under a magnetic field:
after the ZnPc prepared in the example 3 and the bowl-shaped ISP composite functional nanoparticle obtained in the example 4 are illuminated by a 665nm light source, active oxygen is generated to induce apoptosis. The oxygen can react with tris (4, 7-biphenyl-1, 10-phenanthroline) ruthenium dichloride, so that the fluorescence intensity is reduced. The experimental steps are as follows, Hela cells are inoculated into a culture plate, after 24h, DMEM solution of ZnPc and bowl-shaped ISP composite functional nanoparticles with phthalocyanine concentration of 0.7 mu g/mL respectively is prepared, 5uM of tris (4, 7-biphenyl-1, 10-phenanthroline) ruthenium dichloride is added after the cells are incubated for 4h, and after incubation for 1h, illumination is carried out to observe fluorescence intensity.
As shown in fig. 7, tris (4, 7-biphenyl-1, 10-phenanthroline) dichloride ruthenium is an oxygen detection probe, and has fluorescence, and after reacting with oxygen, the fluorescence intensity is reduced, and the reduction of the fluorescence intensity is inversely proportional to the oxygen generation capacity. As shown in FIG. 7, the bowl-shaped ISP complex functional nanoparticles can catalyze H in cells under the same experimental conditions2O2The oxygen is generated, the fluorescence intensity of tris (4, 7-biphenyl-1, 10-phenanthroline) ruthenium dichloride is reduced, and the oxygen generating effect of the bowl-shaped ISP composite functional nanoparticles with the external magnetic field is better due to higher content, so that the fluorescence intensity of tris (4, 7-biphenyl-1, 10-phenanthroline) ruthenium dichloride is lower. In addition, due to the consumption of oxygen in the illumination process of the single ZnPc, the cell is in a hypoxia state, and the highest tris (4, 7-biphenyl-1, 10-phenanthroline) ruthenium dichloride is. Therefore, after entering cells, the bowl-shaped ISP composite functional nano particle has the effects of improving the activity of the photosensitizer and improving the targeting property of the photosensitizer.
Example 7
The in vitro photosensitive antitumor activity was tested using the MTT method:
ZnPc and bowl-shaped ISP functional composite nanoparticles and photosensitive antitumor activity of an external magnetic field are compared, the ZnPc and bowl-shaped ISP functional composite nanoparticles are respectively prepared into DMEM solution with the concentration of 0.7 mu g/mL (measured by phthalocyanine concentration), the DMEM solution is added into the plated Hela cell strain, a group of bowl-shaped ISP functional composite nanoparticles solution is added with a magnet under the plate, after the drug incubation is carried out for 4h, the illumination is carried out for 10min by using a 665nm light source, after the incubation is carried out for 24h, the cell survival rate is detected by using an MTT method.
As shown in fig. 8, the experimental results show that the bowl-shaped ISP functional composite nanoparticle has higher anti-tumor activity than ZnPc alone, which indicates that the bowl-shaped ISP functional composite nanoparticle of the present invention has the function of improving the activity of a photosensitizer, and the effect is more obvious after a magnetic field is applied, thus indicating that the bowl-shaped ISP functional composite nanoparticle prepared by the embodiment of the present invention has the effect of improving PDT therapeutic activity.
Example 8
And (3) detecting the in vivo anticancer activity:
in a mouse transplanted tumor model animal body, the ZnPc, bowl-shaped ISP functional composite nano particles and the tumor inhibition capability of the bowl-shaped ISP functional composite nano particles after an external magnetic field are compared and tested. The experimental procedure is as follows, using phthalocyanine concentration as standard, using phosphate buffer solution with pH 7.4 to prepare drug solution with concentration of 3.2mg/kg, respectively injecting ZnPc and bowl-shaped ISP functional composite nano particles into tumor-bearing mice through tail vein, and the dosage of each mouse is 200 μ L. When the administration is finished, a group of mice injected with bowl-shaped ISP functional composite nanoparticles are placed in a fixer, a magnet is attached to a tumor part for targeting, and the tumor position is illuminated after 6 hours of administration.
As shown in fig. 9, the results of the research on the antitumor activity in the mouse transplanted tumor model animal body showed that the change rate of the tumor volume of the mice injected with ZnPc and bowl-shaped ISP functional composite nanoparticles was significantly reduced compared to the blank control group, which proves that both ZnPc and bowl-shaped ISP functional composite nanoparticles inhibit the tumor growth. The change of the tumor volume of the bowl-shaped ISP functional composite nano particles is further inhibited by the external magnetic field, which shows that the external magnetic field improves the enrichment of the bowl-shaped ISP functional composite nano particles in tumor parts, thereby improving the therapeutic activity of the photosensitizer.
Example 9
In vivo nuclear magnetic imaging detection
And (3) carrying out a targeted capability comparison test before and after the bowl-shaped ISP functional composite nano particles are applied with a magnetic field in a mouse transplanted tumor model animal body. The experimental procedure is as follows, bowl-shaped ISP functional composite nano particles are prepared into 0.32mg/mL drug solution by phosphate buffer solution with pH 7.4, and the drug solution is administrated into two groups of tumor-bearing nude mice by tail vein injection in the amount of 200 mu L/mouse, wherein the second group is small group injected with bowl-shaped ISP functional composite nano particlesThe mouse is placed in a fixer, and a magnet is attached to the tumor part for targeting and adding the magnet for 1 h. Two groups of mice take nuclear magnetic imaging pictures of the two groups of mice at 0h and 24h respectively. As shown in FIG. 10, T in nude mouse graft tumor model animal2The research result of the model nuclear magnetic imaging shows that the tumor targeting of the single bowl-shaped ISP functional composite nano particle is weaker than that of the bowl-shaped ISP functional composite nano particle passing through an external magnetic field, which shows that the bowl-shaped ISP functional composite nano particle has good magnetic targeting.
Example 10
Example 10 was prepared identically to example 4, except that: the bowl-shaped structure PEG-b-PS and Fe in the step (3)3O4The mass ratio of ZnPc is 2:1.5: 0.5.
Example 11
Example 11 was prepared identically to example 4, except that: the bowl-shaped structure PEG-b-PS and Fe in the step (3)3O4And the mass ratio of ZnPc is 3:2.2: 1.5.
Claims (10)
1. The bowl-shaped ISP composite functional nano particle is characterized in that a bowl-shaped structure is self-assembled by block polymers and then Fe is loaded3O4Particles and photosensitizer ZnPc; the block polymer is polyethylene glycol block polystyrene (PEG-b-PS).
2. The bowl-shaped ISP composite functional nanoparticle according to claim 1, wherein the bowl-shaped ISP composite functional nanoparticle is of a bowl-shaped structure, Fe3O4The nano particles are loaded in the groove of the bowl-shaped structure to form a functional nano carrier with magnetic targeting, and then the ISP functional composite nano particles are obtained by loading a photosensitizer ZnPc.
3. The bowl-shaped ISP complex functional nanoparticle which is characterized in that the bowl-shaped ISP complex functional nanoparticle is an organic-inorganic complex nanoparticle suitable for intravenous injection.
4. The preparation method of the bowl-shaped ISP functional composite nano particle disclosed by claim 1, which is characterized by comprising the following steps:
(1) synthesizing and self-assembling preparing PEG-b-PS with a bowl-shaped structure: dissolving PEG-OH in tetrahydrofuran uniformly, and dissolving in N2Protection and ice water bath, adding 2-bromine isobutyryl bromide for reaction, filtering the product, and using NaHCO as supernatant3Extracting the solution, and drying in vacuum to obtain a PEG-Br macromolecular initiator; dissolving a PEG-Br macromolecular initiator in anisole to dissolve, adding styrene, CuCl and PMDETA to react, purifying and separating a product, carrying out reduced pressure distillation and concentration on the obtained solution, then settling in a methanol solution, carrying out suction filtration on the precipitate, and carrying out vacuum drying to obtain a polyethylene glycol block polystyrene polymer, namely PEG-b-PS; dissolving PEG-b-PS in a mixed solution of 1, 4-dioxane and tetrahydrofuran, and injecting double distilled water to obtain a PEG-b-PS solution with a bowl-shaped structure;
(2) superparamagnetic Fe3O4And (3) synthesis of nanoparticles: mixing Fe (acac)3Dissolving in triethylene glycol, and synthesizing superparamagnetic Fe by thermal decomposition method3O4A nanoparticle solution;
(3) preparing bowl-shaped ISP functional composite nanoparticles: fe modified by triethylene glycol3O4Mixing the nanoparticle solution with the PEG-b-PS solution with a bowl-shaped structure, and making Fe by the similar intermiscibility of the structures between triethylene glycol and PEG3O4Loading nano particles into PEG-b-PS with a bowl-shaped structure, and obtaining the loaded Fe by centrifugal separation after ultrasonic treatment3O4And adding a ZnPc solution into the nano particles with the bowl-shaped PEG-b-PS structure of the nano particles, mixing, and performing centrifugal separation after ultrasonic treatment to obtain the bowl-shaped ISP functional composite nano particles.
5. The preparation method according to claim 4, wherein the PEG-Br is dissolved in anisole in the step (1), and the addition of styrene, CuCl and PMDETA is carried out in the mixture under anhydrous and anaerobic conditions at 80-100 ℃ overnight; and (2) during feeding of the PEG-Br and the styrene in the step (1), keeping the low-temperature state of the raw materials by placing the reaction container in an ice-water bath.
6. The method of claim 4, wherein the step (2) of synthesizing superparamagnetic Fe by thermal decomposition3O4The nano particle solution is Fe (acac)3After dissolving uniformly in triethylene glycol, N2Under protection, the temperature is increased to 200 ℃, 250 ℃ and 280 ℃ in a gradient way, and the superparamagnetic Fe is obtained after reflux reaction for 0.5 to 1 hour at 280 DEG C3O4A nanoparticle solution.
7. The method according to claim 6, wherein the step (2) of gradient heating is maintained at 200 ℃ and 250 ℃ for 5-10min, respectively.
8. The method according to claim 4, wherein the PEG-b-PS and Fe in step (3)3O4The mass ratio of ZnPc is 2-3:1.5-2.2: 0.5-1.5.
9. Use of the bowl-shaped ISP functional composite nanoparticle of claim 1 in preparation of photodynamic medicaments.
10. The use of claim 10, wherein the bowl-shaped ISP functional composite nanoparticles are used as photosensitizers and carriers in the preparation of photodynamic medicaments.
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|---|---|---|---|---|
| CN112724898A (en) * | 2020-12-25 | 2021-04-30 | 深圳市南科康达科技有限公司 | Epoxy resin composition and preparation method and application thereof |
| CN114717542A (en) * | 2022-04-02 | 2022-07-08 | 湖南理东科技有限公司 | Bowl-shaped titanium alloy surface modification method for photocatalysis and photo-thermal dual-mechanism antibiosis |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105833293A (en) * | 2015-12-30 | 2016-08-10 | 沈阳药科大学 | Novel nanometer diagnosis and treatment micelle and use thereof |
-
2019
- 2019-12-11 CN CN201911265338.9A patent/CN110917349B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105833293A (en) * | 2015-12-30 | 2016-08-10 | 沈阳药科大学 | Novel nanometer diagnosis and treatment micelle and use thereof |
Non-Patent Citations (3)
| Title |
|---|
| JINGLEI QIN等: "Facile synthesis of dual-functional nanoparticles co-loaded with ZnPc/Fe3O4 for PDT and magnetic resonance imaging", 《MATERIALS RESEARCH BULLETIN》 * |
| YINGFENG TU等: "Biodegradable Hybrid Stomatocyte Nanomotors for Drug Delivery", 《ACS NANO》 * |
| 周林等: "纳米马达在光动力疗法肿瘤治疗中的应用研究", 《第十一届全国化学生物学学术会议》 * |
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|---|---|---|---|---|
| CN112724898A (en) * | 2020-12-25 | 2021-04-30 | 深圳市南科康达科技有限公司 | Epoxy resin composition and preparation method and application thereof |
| CN114717542A (en) * | 2022-04-02 | 2022-07-08 | 湖南理东科技有限公司 | Bowl-shaped titanium alloy surface modification method for photocatalysis and photo-thermal dual-mechanism antibiosis |
| CN114717542B (en) * | 2022-04-02 | 2024-05-03 | 理东新材料科技(山东)有限公司 | Bowl-shaped titanium alloy surface modification method with photocatalysis and photo-thermal dual mechanism antibacterial function |
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