CN111704722A - Preparation method and application of zeolite imidazole type metal organic framework material with polyethylene glycol as mineralizer - Google Patents
Preparation method and application of zeolite imidazole type metal organic framework material with polyethylene glycol as mineralizer Download PDFInfo
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Abstract
The invention relates to a preparation method and application of a zeolite imidazole type metal organic framework material with polyethylene glycol as a mineralizer. According to the invention, the ZIF-8 is prepared by using polyethylene glycol as a mineralizer under mild conditions, and the obtained ZIF-8 nanoparticles have the advantages of good water dispersibility, good stability, controllable particle size and the like, can realize the encapsulation and controllable release of anticancer drug adriamycin, and have very important application value for expanding the delivery field of ZIF-8 in drugs, proteins and other therapeutic agents.
Description
Technical Field
The invention relates to a preparation method and application of a zeolite imidazole type metal organic framework material with polyethylene glycol as a mineralizer, belonging to the technical field of colloidal materials.
Background
The process by which organisms construct organic-inorganic composites by selectively drawing in foreign inorganic matter is called biomineralization. Biomineralization is used as a functional strategy in the process of biological evolution, so that organisms can adapt to the environment better, an evolutionary chain which is more favorable for self development is generated, and a reference direction is provided for regulation and control of the organisms by human beings through materials. The biomineralization material is an organic-inorganic composite material with a highly ordered hierarchical structure and special biological functions, and widely exists in nature, such as teeth, bones, shells, scales, gorgeous corals and the like of various animals. The composite material has various excellent biological properties such as mechanical support, self protection, self-repairing of environmental responsiveness, structural change of environmental responsiveness and the like, and plays a very important role in a living body. Through research on biomineralization, on the basis of deep understanding of the forming process of biomineral materials, people utilize various biomacromolecules as a regulation and control matrix to prepare a series of organic-inorganic composite nano materials. Biomineralization is to use biomineralization in material design, for example, various biomacromolecules such as protein, saccharide, DNA, polypeptide, and amino acid are used as mineralizers to regulate the formation of inorganic minerals, so as to obtain a series of composite nanomaterials with specific structures.
The Metal Organic Framework (MOF) is a porous material formed by coordination of organic ligands and metal ions or metal clusters, and the zeolite imidazole type metal organic framework (ZIF) is a subclass of the MOF and mainly comprises Zn2+、Co2+The MOF has the advantages of good biocompatibility, large specific surface area, controllable composition structure, high porosity, easy surface modification and the like, so that the MOF has very wide application in the fields of biomimetic mineralization and the like.
Proteins are important components of living bodies and are also a very typical organic regulatory matrix in the biomineralization process. However, proteins are affected by their special structures, often have poor stability, are easy to inactivate, and are not easy to store for a long time, which greatly limits their application in various fields. The protein is used as a mineralizer and is encapsulated inside to form the nano-particles with the ZIF-8 crystal structure, so that the thermal stability and the chemical stability of the protein are greatly improved, and a new thought is provided for efficient storage and transportation of biomacromolecules. When the protein is mineralized to form ZIF-8, the drug molecules can be encapsulated to construct a drug delivery carrier. However, ZIF-8 constructed using protein as a mineralizer has disadvantages such as poor stability in aqueous solution, easy aggregation, and difficulty in controlling particle size, and thus, has limited the application of mineralizer in the biomedical field. Therefore, a mineralizer replacing protein is searched, and the application value of the ZIF-8 in the delivery field of protein, medicaments and other therapeutic agents is very important for regulating and controlling the physicochemical properties (such as stability and dispersibility in aqueous solution) of the ZIF-8 and expanding the ZIF-8.
Disclosure of Invention
Aiming at the defects of poor stability, easy aggregation, difficult control of particle size and the like of protein mineralized ZIF-8, the invention provides a preparation method and application of a zeolite imidazole type metal organic framework material taking polyethylene glycol as a mineralizer.
According to the invention, polyethylene glycol is used as a mineralizer, the ZIF-8 nanoparticles with regular dodecahedron morphology and controllable size are prepared under mild conditions, the dispersibility and stability of the particles in an aqueous solution are greatly improved, and meanwhile, the particles can be used as a carrier to encapsulate drug molecules, so that drug-loaded ZIF-8 nanoparticles are obtained; the introduction of polyethylene glycol realizes the regulation and control of the physical and chemical properties of ZIF-8, thereby increasing the efficiency of drug delivery.
In order to solve the problems, the invention is realized by the following technical scheme:
the zeolite imidazole type metal organic framework material with polyethylene glycol as a mineralizer has controllable particle size of 60-600nm, good dispersibility in aqueous solution, and complete morphology structure after being placed in a cell culture solution for 14 days.
A method for preparing ZIF-8 by using polyethylene glycol as a mineralizer comprises the following steps:
dissolving polyethylene glycol in a 2-methylimidazole water solution, filtering to obtain a solution 1, dissolving zinc nitrate in water, filtering to obtain a solution 2, pouring the solution 1 into the solution 2, uniformly mixing and reacting for 15-30 minutes in a rotating manner, and centrifuging, washing and freeze-drying a reaction product to obtain the ZIF-8 nano-particles taking the polyethylene glycol as a mineralizer.
According to the invention, the preferable polyethylene glycol is 8-arm-PEG-OH, the molecular weight is 40kDa, and the concentration of the polyethylene glycol in the solution 1 is 2.5-250 mg mL-1。
Preferably according to the invention, the concentration of 2-methylimidazole in solution 1 is 140-180 mM; most preferably, the concentration of 2-methylimidazole in solution 1 is 160 mM.
Preferably, according to the invention, the concentration of zinc nitrate in solution 2 is 20-60mM, most preferably the concentration of zinc nitrate in solution 2 is 40 mM.
According to the invention, the volume ratio of the solution 1 to the solution 2 is preferably (1-2): (1-2), and most preferably, the volume ratio of the solution 1 to the solution 2 is 1: 1.
According to the invention, the filtration is preferably performed by using a filter membrane with the pore diameter of 0.45 μm.
Preferably, according to the invention, the centrifugation is carried out at a speed of 6000-8000 g.
According to the invention, the product after centrifugation is washed 2 times with water and then 2 times with methanol.
The second purpose of the invention is to provide an application of ZIF-8 taking polyethylene glycol as a mineralizing agent.
Use of ZIF-8 with polyethylene glycol as mineralizer for encapsulating protein or as carrier of medicine is provided.
According to the invention, the preferable specific application method is as follows:
dissolving polyethylene glycol in a 2-methylimidazole aqueous solution, filtering to obtain a solution 1, dissolving a drug in a zinc nitrate aqueous solution, filtering to obtain a solution 2, pouring the solution 1 into the solution 2, uniformly mixing and reacting for 15-30 minutes in a rotating manner, centrifuging, washing and freeze-drying a reaction product to obtain the drug-loaded ZIF-8 nano-particles (DOX @ ZIF-8).
Preferably, according to the invention, the drug is Doxorubicin (DOX).
Preferably, according to the invention, the concentration of the drug in solution 2 is 0.5-2mg mL-1。
According to the invention, the polyethylene glycol is used as a mineralizer to prepare the ZIF-8, and during the construction process, the polyethylene glycol molecules can enrich zinc ions in the solution, so that the nucleation process of the ZIF-8 is accelerated, and the ZIF-8 nanoparticles are quickly coated with the polyethylene glycol molecules. Because the polyethylene glycol has good hydrophilicity, the surface of the nano carrier forms a hydration layer by modifying polyethylene glycol molecules, thereby reducing aggregation among particles and improving the stability of the carrier. Therefore, the introduction of polyethylene glycol can enable the ZIF-8 nanoparticles to have very good dispersibility and stability.
The ZIF-8 taking polyethylene glycol as a mineralizer has the following technical characteristics and advantages:
1. the ZIF-8 taking the polyethylene glycol as the mineralizer has very good dispersibility and stability.
2. The preparation method can realize the regulation and control of the ZIF-8 particle size by changing the reaction temperature or the conditions of the reaction concentration, the molecular weight and the like of polyethylene glycol, thereby preparing a series of ZIF-8 nano-particles with different sizes. And the preparation condition is mild, the synthesis method is quick and simple, and the large-scale production can be realized.
3. The invention takes polyethylene glycol as a mineralizer, greatly improves the dispersibility of ZIF-8 nanoparticles, can store the product in a powder form after freeze-drying, has good redispersibility, and has very important significance for the storage and transportation of nano-drug carriers.
4. The invention takes polyethylene glycol as a mineralizer, and can obviously increase the stability of ZIF-8 nano particles, thereby improving the utilization rate of the medicine and preventing toxic and side effects caused by the early leakage of the medicine.
5. The ZIF-8 drug-loaded nano-particles prepared by encapsulating the anticancer drug DOX by using the polyethylene glycol as a mineralizer have high drug encapsulation rate, can realize drug slow release at tumor parts through pH responsiveness, and have important significance for reducing the toxic and side effects of chemotherapeutic drug molecules.
Drawings
FIG. 1 is a schematic diagram of a process for obtaining drug-loaded ZIF-8 nanoparticles (DOX @ ZIF-8) by encapsulating DOX with 8-arm-PEG-OH as a mineralizer.
FIG. 2 is an SEM photograph and thermogravimetric analysis data of ZIF-8 prepared using polyethylene glycol as a mineralizer, wherein a is an SEM photograph and b is a thermogravimetric analysis data photograph.
FIG. 3 is an SEM image of ZIF-8 nanoparticles prepared with varying concentrations of 8-arm-PEG-OH as mineralizer; in FIGS. 3a, 3b, 3c, 3d, 3e, 3f, 3g and 3h, the concentration of 8-arm-PEG-OH (40kDa) used for preparing ZIF-8 was 1.25mg mL each-1、2.5mg mL-1、5mg mL-1、10mg mL-1、25mg mL-1、50mg mL-1、100mg mL-1And 200mg mL-1。
FIG. 4 is an SEM photograph of ZIF-8 nanoparticles prepared using 8-arm-PEG-OH with different molecular weights as a mineralizer, 4a is an SEM photograph of ZIF-8 nanoparticles prepared using 8-arm-PEG-OH with a molecular weight of 10kDa as a mineralizer, 4b is an SEM photograph of ZIF-8 nanoparticles prepared using 8-arm-PEG-OH with a molecular weight of 20kDa as a mineralizer, wherein the concentrations of 8-arm-PEG-OH are all 2.5mg mL/L-1。
FIG. 5 shows the reaction of 8-arm-PEG-OH (40kDa,5mg mL) at different temperatures-1) TEM images of the resulting ZIF-8 nanoparticles prepared for the mineralizer; in FIGS. 5a, 5b, 5c, 5d, 5e and 5f, the reaction temperatures for preparing ZIF-8 were 10 deg.C, 20 deg.C, 30 deg.C, 40 deg.C, 50 deg.C and 70 deg.C, respectively.
FIGS. 6a, 6b and 6c are respectively a sample taken from 8-arm-PEG-OH (40kDa,2.5mg mL)-1) SEM images obtained after mixing ZIF-8 prepared for the mineralizer with the cell culture medium (containing 10% fetal bovine serum) for 1 day, 4 days, and 14 days, and fig. 6d is an SEM image taken after conventional ZIF-8 nanoparticles (without mineralizer) were placed in an aqueous solution for one day.
FIG. 7 shows a sample of 8-arm-PEG-OH (40kDa,2.5mg mL)-1) Is a mineralizer, and encapsulates DOX to obtain the cytotoxicity experimental result of the drug-loaded ZIF-8 nano-particles.
FIG. 8 is a confocal laser microscopy image of DOX @ ZIF-8 co-cultured with Hela cells for 4h, taken after staining the cells.
The specific implementation mode is as follows:
for a better understanding of the present invention, reference is made to the following detailed description and accompanying drawings.
Example 1
The preparation of ZIF-8 using polyethylene glycol as mineralizer comprises the following steps:
dissolving 8-arm-PEG-OH with the molecular weight of 40kDa in 2-methylimidazole water solution, performing ultrasonic dissolution, and filtering with a filter membrane with the pore diameter of 0.45 mu m to obtain solution 1; the concentration of polyethylene glycol in solution 1 was 2.5mg mL-1The concentration of 2-methylimidazole is 160 mM;
dissolving zinc nitrate in water, and filtering to obtain a solution 2, wherein the concentration of the zinc nitrate in the solution 2 is 40 mM;
and pouring the solution 1 into the solution 2 with the same volume, placing the solution on a rotary blending machine for reaction for 30min, centrifuging the obtained product, washing the product twice with water and twice with methanol, and freeze-drying the product to obtain the ZIF-8 nano-particles taking polyethylene glycol as a mineralizer.
An SEM image and thermogravimetric analysis data of ZIF-8 prepared by using polyethylene glycol as a mineralizer are shown in FIG. 1. As can be seen from the SEM characterization results of FIG. 1, the ZIF-8 nanoparticles were regular dodecahedral structures having a uniform particle size, and the average particle size was 240 nm.
Experimental example 1
1. Particle size control of ZIF-8 by varying the concentration of polyethylene glycol
Weighing different masses of 8-arm-PEG-OH (40kDa) and dissolving in 2-methylimidazole water solution, ultrasonically dissolving, and filtering with a filter membrane with the pore diameter of 0.45 μm to obtain solutions 1 (the concentration of 2-methylimidazole is 160mM) with different polyethylene glycol concentrations; adding the solution 1 into an aqueous solution of zinc nitrate (40mM) with the same volume, reacting on a rotary mixer for 30min, centrifuging, washing twice with water, and washing twice with methanol; and respectively dripping 4 mu L of ZIF-8 nano particles dispersed in methanol on a cleaned silicon wafer, and carrying out SEM test after the methanol is completely volatilized and gold is sprayed. The particle sizes of ZIF-8 nanoparticles prepared at various concentrations of 8-arm-PEG-OH (40kDa) are shown in Table 1, and the SEM characterization data are shown in FIG. 3.
Statistical results prove that the larger the concentration of 8-arm-PEG-OH (40kDa), the smaller the particle size of the finally obtained ZIF-8 nano-particles, so that the regulation and control of the ZIF-8 particle size can be realized by changing the reaction concentration of polyethylene glycol.
TABLE 1 particle size of ZIF-8 nanoparticles prepared with different concentrations of 8-arm-PEG-OH (40kDa) as mineralizer
2. Particle size of ZIF-8 was controlled by varying the molecular weight of polyethylene glycol
Respectively dissolving 8-arm-PEG-OH with different molecular weights (10kDa or 20kDa) in 2-methylimidazole water solution, ultrasonically dissolving, and filtering with filter membrane with pore diameter of 0.45 μm to obtain solution 1 (2-methylimidazole concentration of 160mM, 8-arm-PEG-OH concentration of 2.5mg mL) with different polyethylene glycol molecular weights-1) (ii) a Adding the solution 1 into an equal volume of zinc nitrate (40mM) aqueous solution, reacting on a rotary mixer for 30min, taking down, centrifuging, and washing with water and methanol respectively. And respectively dripping 4 mu L of ZIF-8 nano particles dispersed in methanol on a clean silicon chip, and carrying out SEM test after the methanol is completely volatilized and gold is sprayed.
The average particle sizes of ZIF-8 nanoparticles prepared by using 8-arm-PEG-OH with different molecular weights (10kDa or 20kDa) as a mineralizer are respectively 160nm and 200nm, and SEM characterization data are shown in figure 4. It can be concluded that compared to ZIF-8 nanoparticles (particle size 240nm) prepared with 8-arm-PEG-OH having a molecular weight of 40kDa as mineralizer as shown in fig. 2: the lower the molecular weight of 8-arm-PEG-OH, the particle size of the resulting ZIF-8 nanoparticles would be significantly reduced. Therefore, the particle size of the ZIF-8 nanoparticles can be controlled by using polyethylene glycols of different molecular weights as mineralizers.
3. Particle size control of ZIF-8 by varying reaction temperature
Dissolving 8-arm-PEG-OH with the molecular weight of 40kDa in 2-methylimidazole water solution, performing ultrasonic dissolution, and filtering with a filter membrane with the pore diameter of 0.45 mu m to obtain solution 1; the concentration of polyethylene glycol in solution 1 was 5mg mL-1The concentration of 2-methylimidazole is 160 mM; adding the solution 1 into an equal volume of zinc nitrate (40mM) aqueous solution, placing the mixture in water baths of different temperatures (10 ℃, 20 ℃, 30 ℃, 40 ℃, 50 ℃ and 70 ℃) and stirring by using magnetic force, reacting for 30min, centrifuging the product, and washing with water and methanol respectively. And (5) preparing a sample, and then performing TEM test. In different reactionsThe particle sizes of the ZIF-8 nanoparticles obtained at temperature are shown in Table 2, and TEM characterization data are shown in FIG. 5.
Statistical results prove that the particle size of the ZIF-8 nanoparticles is gradually reduced with the increase of the reaction temperature, so that the particle size of the ZIF-8 nanoparticles can be regulated and controlled by changing the reaction temperature.
TABLE 2 particle size of ZIF-8 nanoparticles prepared at different reaction temperatures
4. Stability of ZIF-8 nano-drug carrier prepared by taking polyethylene glycol as mineralizer
The ZIF-8 nanoparticles prepared in example 1 were placed in a cell culture medium and the stability thereof was examined. As can be seen in FIG. 6c, the ZIF-8 retains the intact morphology after being blended with the cell culture medium for 14 days; it can be seen from fig. 6d that conventional ZIF-8 nanoparticles (not using polyethylene glycol as a template mineralizer) rapidly degrade after one day in aqueous solution. Therefore, the stability of the ZIF-8 nanoparticles can be greatly improved by using polyethylene glycol as a mineralizer.
Example 2
A method for preparing drug-loaded ZIF-8 nanoparticles (DOX @ ZIF-8) by taking polyethylene glycol as a mineralizer comprises the following steps:
dissolving 8-arm-PEG-OH with the molecular weight of 40kDa in 2-methylimidazole water solution, performing ultrasonic dissolution, and filtering with a filter membrane with the pore diameter of 0.45 mu m to obtain solution 1; the concentration of polyethylene glycol in solution 1 was 2.5mg mL-1The concentration of 2-methylimidazole is 160 mM;
weighing DOX, dissolving in zinc nitrate water solution, filtering with filter membrane to obtain solution 2, wherein the concentration of zinc nitrate in solution 2 is 40mM, and the concentration of DOX is 0.5mg mL-1。
And pouring the solution 1 into the solution 2 with the same volume, placing the solution on a rotary mixer for reaction for 30min, centrifuging the obtained product, washing the product twice with water and twice with methanol, and freeze-drying the product to obtain the drug-loaded ZIF-8 nano particles (DOX @ ZIF-8).
Experimental example 2
1. DOX encapsulation quantification
Weighing 2mg of drug-loaded ZIF-8 nanoparticles, and adding 10mL of CH3COONa buffer (50mM, pH 5.5), reacting for 30min, centrifuging without precipitation, which indicates that ZIF-8 degradation is complete and DOX is completely released. The ultraviolet absorption spectrum is measured, and according to the ultraviolet absorption standard curve of DOX, the DOX @ ZIF-8 per milligram approximately contains 51.5 mu g of DOX, and the drug loading efficiency is 5%.
2. Cytotoxicity test
8000 HeLa cells were plated per well in a 96-well plate and cultured overnight in a thermostatted carbon dioxide incubator to adhere the cells to the wall. Concentrations of DOX were set to 0.25, 1.5, 2, 2.75, 3.25 and 4. mu.g mL, respectively-15 replicate wells were set for each concentration, and 100. mu.L of a mixture of drug and cell culture medium at the corresponding concentration was added to each well. After 20 hours of incubation, 10 μ LMTT (5mg mL) was added to each well-1) The incubation was continued for 4 hours. Then, the liquid in each well was aspirated, 100. mu.L of DMSO was added to dissolve formazan, and the absorbance at an excitation wavelength of 570nm was measured with a microplate reader. The test results are shown in FIG. 7, and the IC of free DOX and DOX @ ZIF-8 is obtained by calculation50The values were 3.1. mu.g mL, respectively-1And 2.3. mu.g mL-1. It is demonstrated that DOX @ ZIF-8 has a stronger killing effect on cells than free DOX at the same DOX concentration.
3. Confocal imaging
500 microliter of cell culture medium is added into each hole of the 4-hole confocal dish, the cell density is 5 ten thousand per hole, and the cells are cultured in a constant temperature incubator overnight to adhere to the wall. The medium was decanted and 500. mu.L of cell culture medium containing DOX @ ZIF-8 (DOX concentration 2. mu.g mL) was added to each well-1) And then cultured in a constant temperature incubator for 4 hours. Then the liquid was aspirated, PBS was washed once, 500. mu.L of paraformaldehyde (4%) was added to each well to fix the cells for 15min, paraformaldehyde was aspirated off, PBS was washed once, and 500. mu.L of LHoechst dye (1. mu.g mL) was added-1) The nuclei were stained for 10min, blotted and washed once with PBS, and finally 500. mu.L WGA488 dye (5. mu.g mL) was added-1) Staining the cell membrane for 10min, washing with PBS onceThen, the cells were imaged by confocal laser microscopy, and the image of the cells was shown in FIG. 8.
As can be seen from a confocal microscope photo, DOX @ ZIF-8 and cells can be internalized by the cells after being co-cultured for 4 hours, and part of the drug enters cell nucleus, so that the drug-loaded nanoparticle is proved to have better internalization capability.
Claims (10)
1. The zeolite imidazole type metal organic framework material with polyethylene glycol as a mineralizer has controllable particle size of 60-600nm, good dispersibility in aqueous solution, and complete morphology after being placed in a cell culture solution for 14 days.
2. A method for preparing ZIF-8 using polyethylene glycol as a mineralizer, comprising the steps of:
dissolving polyethylene glycol in a 2-methylimidazole water solution, filtering to obtain a solution 1, dissolving zinc nitrate in water, filtering to obtain a solution 2, pouring the solution 1 into the solution 2, uniformly mixing and reacting for 15-30 minutes in a rotating manner, and centrifuging, washing and freeze-drying a reaction product to obtain the ZIF-8 material based on polyethylene glycol.
3. The method according to claim 2, wherein the polyethylene glycol is 8-arm-PEG-OH, the molecular weight is 40kDa, and the concentration of the polyethylene glycol in the solution 1 is 2.5-250 mg mL-1The concentration of 2-methylimidazole in the solution 1 is 140-180 mM; most preferably, the concentration of 2-methylimidazole in solution 1 is 160 mM.
4. The method of claim 2, wherein the concentration of zinc nitrate in solution 2 is 20 to 60mM, and most preferably the concentration of zinc nitrate in solution 2 is 40 mM.
5. The method according to claim 2, wherein the volume ratio of the solution 1 to the solution 2 is (1-2): (1-2), and most preferably, the volume ratio of the solution 1 to the solution 2 is 1: 1.
6. The method as claimed in claim 2, wherein the filtration is performed by using a filter membrane with a pore size of 0.45 μm, the centrifugation speed is 6000-8000g, and the washing is performed by washing the centrifuged product with water for 2 times and then with methanol for 2 times.
7. Use of ZIF-8 with polyethylene glycol as mineralizer for encapsulating protein or as carrier of medicine is provided.
8. The application of claim 7, wherein the specific application method is as follows:
dissolving polyethylene glycol in a 2-methylimidazole aqueous solution, filtering to obtain a solution 1, dissolving a drug in a zinc nitrate aqueous solution, filtering to obtain a solution 2, pouring the solution 1 into the solution 2, uniformly mixing and reacting for 15-30 minutes in a rotating manner, centrifuging, washing and freeze-drying a reaction product to obtain the drug-loaded ZIF-8 nano-particles (DOX @ ZIF-8).
9. The use of claim 7, wherein said drug is Doxorubicin (DOX).
10. The use of claim 7, wherein the concentration of drug in solution 2 is 0.5-2mg mL-1。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN202010461645.0A CN111704722B (en) | 2020-05-27 | 2020-05-27 | Preparation method and application of zeolite imidazole type metal organic framework material with polyethylene glycol as mineralizer |
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| CN111592661A (en) * | 2020-06-16 | 2020-08-28 | 南京邮电大学 | Preparation method of high-dispersity organic metal framework nano material |
| CN113171754A (en) * | 2021-04-27 | 2021-07-27 | 郑州大学 | Hierarchical porous metal organic framework material ZIF-8 and preparation method and application thereof |
| CN114949246A (en) * | 2022-04-21 | 2022-08-30 | 山东大学 | Toll-like receptor agonist nanoparticles and preparation method and application thereof |
| CN115232320A (en) * | 2022-04-27 | 2022-10-25 | 北京工业大学 | Green method for regulating and controlling size and morphology of MOFs crystal by adopting modifier system |
| CN115414488A (en) * | 2022-09-14 | 2022-12-02 | 山东大学 | Preparation method and application of targeted polyethylene glycol drug carrier |
| CN117138055A (en) * | 2023-06-02 | 2023-12-01 | 中山大学附属第一医院 | Double-carrier doxorubicin drug-loaded nano material and preparation method thereof |
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| CN109134873A (en) * | 2018-07-31 | 2019-01-04 | 浙江大学 | A method of regulating and controlling ZIF-8 nano-particles size using single-ended amino-polyethyleneglycols |
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| CN111592661A (en) * | 2020-06-16 | 2020-08-28 | 南京邮电大学 | Preparation method of high-dispersity organic metal framework nano material |
| CN113171754A (en) * | 2021-04-27 | 2021-07-27 | 郑州大学 | Hierarchical porous metal organic framework material ZIF-8 and preparation method and application thereof |
| CN113171754B (en) * | 2021-04-27 | 2022-09-27 | 郑州大学 | Hierarchical porous metal organic framework material ZIF-8 and preparation method and application thereof |
| CN114949246A (en) * | 2022-04-21 | 2022-08-30 | 山东大学 | Toll-like receptor agonist nanoparticles and preparation method and application thereof |
| CN114949246B (en) * | 2022-04-21 | 2023-11-14 | 山东大学 | Toll-like receptor agonist nano-particle and preparation method and application thereof |
| CN115232320A (en) * | 2022-04-27 | 2022-10-25 | 北京工业大学 | Green method for regulating and controlling size and morphology of MOFs crystal by adopting modifier system |
| CN115232320B (en) * | 2022-04-27 | 2023-10-27 | 北京工业大学 | Green method for regulating and controlling crystal size and morphology of crystal MOFs by adopting modifier system |
| CN115414488A (en) * | 2022-09-14 | 2022-12-02 | 山东大学 | Preparation method and application of targeted polyethylene glycol drug carrier |
| CN117138055A (en) * | 2023-06-02 | 2023-12-01 | 中山大学附属第一医院 | Double-carrier doxorubicin drug-loaded nano material and preparation method thereof |
| CN117138055B (en) * | 2023-06-02 | 2024-04-16 | 中山大学附属第一医院 | Double-carrier doxorubicin drug-loaded nano material and preparation method thereof |
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