CN114848609B - Drug-loaded ZIF-8 nanoparticle covered with TF-PEG-PLGA coating, and preparation method and application thereof - Google Patents

Drug-loaded ZIF-8 nanoparticle covered with TF-PEG-PLGA coating, and preparation method and application thereof Download PDF

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CN114848609B
CN114848609B CN202210486787.1A CN202210486787A CN114848609B CN 114848609 B CN114848609 B CN 114848609B CN 202210486787 A CN202210486787 A CN 202210486787A CN 114848609 B CN114848609 B CN 114848609B
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CN114848609A (en
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方兴刚
罗杰
郭兴荣
杜士明
汪嫚
柏中喜
马石楠
冯莹
陈卓
李童斐
兰培敏
陈汉玉
鲁军体
张宇强
皇甫沁媛
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Shiyan Taihe Hospital
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Abstract

The invention discloses a drug-loaded ZIF-8 nanoparticle covered with a TF-PEG-PLGA coating, and a preparation method and application thereof, wherein the drug-loaded ZIF-8 nanoparticle comprises the following components: adding a target drug, 2-methylimidazole and zinc nitrate into a methanol solution, mixing, performing a first reaction, and purifying and dissolving in methanol to obtain a drug-loaded ZIF-8 nanoparticle solution; after being activated, the COOH-PEG-PLGA is uniformly mixed with transferrin in PBS for a second reaction, and then purified and dissolved in PBS to obtain a transferrin modified PEG-PLGA solution; and uniformly mixing the drug-carrying ZIF-8 nanoparticle solution and the transferrin modified PEG-PLGA solution to obtain the drug-carrying ZIF-8 nanoparticle covered with the TF-PEG-PLGA coating. The nanoparticle has blood brain barrier permeability, tumor targeting and targeting drug delivery aiming at craniocerebral tumors, and provides an ideal carrier for efficient and targeted drug delivery of intracranial tumors.

Description

Drug-loaded ZIF-8 nanoparticle covered with TF-PEG-PLGA coating, and preparation method and application thereof
Technical Field
The invention relates to the technical field of biomedical detection, in particular to a drug-loaded ZIF-8 nanoparticle covered with a TF-PEG-PLGA coating, and a preparation method and application thereof.
Background
Gliomas are the most common primary tumors in the human central nervous system, accounting for about 80% of all primary malignant brain tumors, wherein Gliobastoma (GBM) is grade IV glioma, accounting for about 54% of the total glioma, and are characterized by high morbidity, high recurrence rate, high fatality rate, and low cure rate. Surgery assisted by radiation therapy and chemotherapy is currently the primary treatment for GBM. However, due to the invasive growth pattern of GBM, surgery is difficult to completely ablate and radiotherapy has problems with radiotherapy resistance. The application of the chemotherapeutic drugs can improve the prognosis of patients with surgery and radiotherapy, and the blood brain barrier penetrating ability of the chemotherapeutic drugs and the toxic and side effects of the chemotherapy restrict the application of the chemotherapeutic drugs in GBM treatment.
The traditional chemotherapy drugs have the problems of permeability of the blood brain barrier and toxic and side effects of the drugs, the breakthrough for solving the problems is to improve the permeability of the blood brain barrier of the drugs and the targeting property of the tumors, the targeted administration of tumor tissues is beneficial to reducing the toxic and side effects of the drugs,
therefore, it is necessary to develop a drug-loaded nanoparticle with blood brain barrier permeability and tumor targeting.
Disclosure of Invention
The invention aims to provide a drug-loaded ZIF-8 nanoparticle covered with a TF-PEG-PLGA coating, a preparation method and application thereof, and the nanoparticle has blood brain barrier permeability, tumor targeting and targeting drug delivery aiming at craniocerebral tumors, provides an ideal carrier for efficient and targeted drug delivery of craniocerebral tumors, and has wide prospect in the aspect of intracranial tumor application.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
in a first aspect of the present invention, there is provided a method for preparing drug-loaded ZIF-8 nanoparticles coated with TF-PEG-PLGA, the method comprising:
adding a target drug, 2-methylimidazole and zinc nitrate into a methanol solution, mixing, performing a first reaction, and purifying and dissolving in methanol to obtain a drug-loaded ZIF-8 nanoparticle solution;
the following operation a or operation B is then performed:
operation a:
after being activated, the COOH-PEG-PLGA is uniformly mixed with transferrin in PBS for a second reaction, and then purified and dissolved in PBS to obtain a transferrin modified PEG-PLGA solution, namely TF-PEG-PLGA;
uniformly mixing the drug-carrying ZIF-8 nanoparticle solution and the transferrin modified PEG-PLGA solution to obtain drug-carrying ZIF-8 nanoparticles covered with a TF-PEG-PLGA coating, namely ZIF-8/Tf-PEG-PLGA;
or operation B:
uniformly mixing the drug-carrying ZIF-8 nanoparticle solution with COOH-PEG-PLGA in PBS, and purifying and dissolving in PBS to obtain drug-carrying @ ZIF-8/PEG-PLGA suspension;
and activating the drug-carrying @ ZIF-8/PEG-PLGA suspension, mixing with transferrin, purifying and dissolving in methanol to obtain drug-carrying ZIF-8 nanoparticles, namely ZIF-8/Tf-PEG-PLGA, which cover the TF-PEG-PLGA coating.
Further, the target drug comprises one of aloe-emodin, cisplatin, paclitaxel and indocyanine green.
Further, the mass ratio of the target drug to the 2-methylimidazole to the zinc nitrate is 1: (15-17): (7-8).
Further, the conditions of the first reaction and the second reaction each include: magnetically stirring at 200-300 rpm, reacting at room temperature for 0.5-2 hr, and standing.
Further, the method for COOH-PEG-PLGA activation comprises: the COOH-PEG-PLGA is activated by adopting 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) to activate carboxyl groups on the COOH-PEG-PLGA.
Further, in both of the operation a and the operation B, the mass ratio of the transferrin to the COOH-PEG-PLGA is 1: (700-800).
Further, in the operation a, the volume ratio of the drug-loaded ZIF-8 nanoparticle solution to the transferrin-modified PEG-PLGA solution is (6 to 8): (2-4); in the operation B, the volume ratio of the drug-loaded ZIF-8 nanoparticle solution to the COOH-PEG-PLGA is (6-8): (2-4).
Further, the method further comprises:
and (3) carrying out centrifugal purification, sterilization and dissolution on the drug-loaded ZIF-8 nano particles covered with the TF-PEG-PLGA coating in the presence of a surfactant.
In a second aspect of the invention, drug-loaded ZIF-8 nanoparticles covering the TF-PEG-PLGA coating, which are prepared by the method, are provided, wherein the nanoparticles have a core-shell structure:
the nuclear layer is ZIF-8 nanoparticles carrying medicine;
and the shell layer is wrapped on the periphery of the core layer, and the shell layer is transferrin modified PEG-PLGA.
In a third aspect of the invention, the application of the drug-loaded ZIF-8 nanoparticles covered with the TF-PEG-PLGA coating in preparing drug-loaded nanoparticle drugs for targeted delivery of craniocerebral tumors is provided.
One or more technical solutions in the embodiments of the present invention at least have the following technical effects or advantages:
according to the invention, a Tf-PEG-PL coating which is coated with an antitumor drug aloe-emodin and an outer coating can enhance the permeability of a drug blood brain barrier by utilizing a tumor targeting ZIF-8 nanoparticle, and the ZIF-8 has the tumor microenvironment release characteristic, so that the targeting of tumors can be realized; transferrin (TF) can bind to transferrin receptor expressed specifically and highly in the blood brain barrier, and penetrate the blood brain barrier in a carrier transport manner, so as to enhance the penetration capacity of the nanoparticle blood brain barrier; the biocompatibility of PLGA is utilized to enhance the water solubility of the medicine on one hand and the blood brain barrier penetrating ability of the medicine on the other hand; the use of polyethylene glycol (PEG-PLGA) can prolong the in vivo circulation time of the drug. The drug-loaded nanoparticle can enhance the blood brain barrier penetration capability of the drug, enhance the tumor targeting capability of the drug, enhance the anti-tumor efficiency of the drug and reduce the toxic and side effects of the drug. Therefore, the invention is expected to have good application prospect in brain tumor targeting administration, and compared with the prior art, the invention has the following beneficial effects:
(1) Enhancing the permeability of the blood brain barrier of the medicine and improving the concentration of the medicine in intracranial tissues.
(2) As shown in FIG. 8, the drug-loaded ZIF-8 nanoparticle covered with the TF-PEG-PLGA coating can improve the drug tumor enrichment and targeting capability, enhance the drug distribution of tumor tissues to reduce the drug distribution of normal tissues, enhance the anti-tumor effect to reduce adverse side effects.
(3) The invention uses nanometer material, which has good biocompatibility and can improve the water solubility, stability and internal circulation time of the medicine.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for the description of the embodiments will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic diagram of AE@ZIF-8/Tf-PEG-PLGA nanoparticle construction;
FIG. 2 is a schematic illustration of nanoparticle in vivo delivery;
FIG. 3 is an external view of a nanoparticle transmission electron microscope;
FIG. 4 is a graph of nanoparticle size;
FIG. 5 is a graph of zeta potential of nanoparticle surfaces;
FIG. 6 is a nanoparticle ultraviolet absorbance spectrum;
FIG. 7 is an in vitro release profile of nanoparticles;
FIG. 8 is a graph of nanoparticle intracranial distribution and tumor enrichment.
Detailed Description
The advantages and various effects of the present invention will be more clearly apparent from the following detailed description and examples. It will be understood by those skilled in the art that these specific embodiments and examples are intended to illustrate the invention, not to limit the invention.
Throughout the specification, unless specifically indicated otherwise, the terms used herein should be understood as meaning as commonly used in the art. Accordingly, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification will control.
Unless specifically indicated otherwise, the various raw materials, reagents, instruments, equipment, etc., used in the present invention are commercially available or may be obtained by existing methods.
The general idea of the invention is as follows:
according to an exemplary embodiment of the present invention, there is provided a method for preparing drug-loaded ZIF-8 nanoparticles coated with TF-PEG-PLGA, the method comprising:
s101, adding a target drug, 2-methylimidazole and zinc nitrate into a methanol solution, mixing, performing a first reaction, and purifying and dissolving in methanol to obtain a drug-loaded ZIF-8 nanoparticle solution;
in the technical proposal, the utility model has the advantages that,
the methanol solution is a pure methanol solution;
the target drug comprises aloe-emodin. In other embodiments, the target drug may also be cisplatin, paclitaxel, indocyanine green;
the mass ratio of the target drug to the 2-methylimidazole to the zinc nitrate is 1: (15-17): (7-8). This mass ratio range is advantageous for achieving the best drug encapsulation efficiency.
The conditions of the first reaction all include: magnetically stirring at 200-300 rpm, reacting at room temperature for 0.5-2 hr, and standing.
As a specific embodiment, the purification mode is centrifugal precipitation washing, washing for three times in a methanol environment at 12000rpm for 10 minutes, taking the precipitate, and carrying out subsequent reactions.
Step S102, after being activated, COOH-PEG-PLGA is uniformly mixed with transferrin in PBS for a second reaction, and then purified and dissolved in PBS to obtain a transferrin modified PEG-PLGA solution, which is called as TF-PEG-PLGA for short;
in the technical proposal, the utility model has the advantages that,
before the modification reaction is carried out on the COOH-PEG-PLGA, the COOH-PEG-PLGA is activated by adopting 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS).
The mass ratio of the transferrin to the COOH-PEG-PLGA is 1: (700-800). The mass ratio range is favorable for obtaining the best transferrin connection rate;
as a specific embodiment, the purification method is that the centrifugal precipitation is washed, and the washing is carried out twice in a methanol environment at 12000rpm for 10 minutes.
Step S103, uniformly mixing the drug-loaded ZIF-8 nanoparticle solution and the transferrin modified PEG-PLGA solution to obtain drug-loaded ZIF-8 nanoparticles covered with TF-PEG-PLGA coating, namely ZIF-8/Tf-PEG-PLGA.
In the technical proposal, the utility model has the advantages that,
the volume ratio of the drug-loaded ZIF-8 nanoparticle solution to the transferrin modified PEG-PLGA solution is (6-8): (2-4). The volume ratio range is favorable for obtaining better drug loading rate, transferrin connection rate and practical nano particle size; if the mass ratio is too large, the adverse effect of reducing the transferrin connection rate is brought about, and if the mass ratio is too small, the prepared nanoparticle has too large particle size, so that the nanoparticle is not suitable for intracranial administration.
The method further comprises the steps of:
and (3) carrying out centrifugal purification, sterilization and dissolution on the drug-loaded ZIF-8 nano particles covered with the TF-PEG-PLGA coating in the presence of a surfactant. The sterilization method is 75% ethanol soaking. The surfactant comprises 1% poloxamer.
According to another exemplary embodiment of the present invention, there is provided a method for preparing drug-loaded ZIF-8 nanoparticles coated with TF-PEG-PLGA, the method comprising:
step S201, adding a target drug, 2-methylimidazole and zinc nitrate into a methanol solution, mixing to perform a first reaction, and purifying and dissolving the mixture in methanol to obtain a drug-loaded ZIF-8 nanoparticle solution;
step S202, uniformly mixing the drug-loaded ZIF-8 nanoparticle solution with COOH-PEG-PLGA in PBS, and purifying and dissolving in PBS to obtain a drug-loaded @ ZIF-8/PEG-PLGA suspension;
in the technical proposal, the utility model has the advantages that,
the volume ratio of the drug-loaded ZIF-8 nanoparticle solution to the COOH-PEG-PLGA is (6-8): (2-4).
Step S203, activating the drug-carrying @ ZIF-8/PEG-PLGA suspension, mixing with transferrin, purifying and dissolving in methanol to obtain drug-carrying ZIF-8 nanoparticles, namely ZIF-8/Tf-PEG-PLGA, which cover the TF-PEG-PLGA coating.
In the above technical scheme, the mass ratio of transferrin to COOH-PEG-PLGA is 1: (700-800).
The drug-loaded ZIF-8 nanoparticle covered with the TF-PEG-PLGA coating, and the preparation method and application thereof are described in detail below with reference to examples and experimental data.
Example 1 drug-loaded ZIF-8 nanoparticle covered with TF-PEG-PLGA coating and preparation method thereof
75mg of zinc nitrate is taken and dissolved in a 2.5ml sample bottle (A bottle), and 120W ultrasonic bath is carried out for 2 minutes for dissolution; 165mg of dimethyl imidazole and 10mg of aloe vera Huang Sugong were dissolved in 5ml of methanol (B flask), dissolved in a 120W ultrasonic bath for 5 minutes, magnetically stirred at room temperature for 5 minutes, 250 revolutions per minute. The bottle A is added into the bottle B drop by drop, and the mixture is stirred for 1 hour under the condition of room temperature and light shielding for 250 minutes/magnetic stirring, and is kept stand for 1 hour at 4 ℃.12000 r/min separating heart, collecting precipitate to obtain AE@ZIF-8 nanoparticle, re-suspending with methanol, centrifuging again, repeating for three times, and re-suspending the final product with 5ml methanol.
10mg COOH-PEG-PLGA was dissolved in 4.5ml Phosphate Buffer (PBS), sonicated at 120W for 5 minutes, and then 1mg/ml 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and 1mg/ml N-hydroxysuccinimide (NHS) were added dropwise, each 250. Mu.L, and magnetically stirred at room temperature for 4 hours, 250 rpm. 1mg/ml transferrin aqueous solution was added dropwise, stirring was continued for 2 hours in the dark, and left standing overnight at 4 ℃.12000 revolutions per minute of heart was isolated for 10 minutes, tf-PEG-PLGA was obtained by precipitation, resuspended in PBS, centrifuged again, and the resultant was repeated three times and resuspended in 5ml PBS.
Mixing the AE@ZIF-8 methanol solution and Tf-PEG-PLGA aqueous solution according to the volume ratio of 7:3, and magnetically stirring for 4 hours at room temperature under the dark condition, wherein the rotation speed is 250 r/min. 12000 rpm/separating heart for 10 min, collecting precipitate to obtain final product AE@ZIF-8/Tf-PEG-PLGA, re-suspending with methanol, and repeating twice for 12000 rpm/separating heart for 10 min. Resuspension with 75% ethanol, soaking for 30 min, centrifuging, and washing the precipitate twice with physiological saline containing 1% poloxamer.
Example 2 drug-loaded ZIF-8 nanoparticle covered with TF-PEG-PLGA coating and preparation method thereof
75mg of zinc nitrate is taken and dissolved in a 2.5ml sample bottle (A bottle), and 120W ultrasonic bath is carried out for 2 minutes for dissolution; 165mg of dimethyl imidazole and 10mg of aloe vera Huang Sugong were dissolved in 5ml of methanol (B flask), dissolved in a 120W ultrasonic bath for 5 minutes, magnetically stirred at room temperature for 5 minutes, 250 revolutions per minute. The bottle A is added into the bottle B drop by drop, and the mixture is stirred for 1 hour under the condition of room temperature and light shielding for 250 minutes/magnetic stirring, and is kept stand for 1 hour at 4 ℃.12000 r/min separating heart, collecting precipitate to obtain AE@ZIF-8 nanoparticle, re-suspending with methanol, centrifuging again, repeating for three times, and re-suspending the final product with 5ml methanol.
10mgCOOH-PEG-PLGA was dissolved in 4.5ml Phosphate Buffer (PBS), sonicated at 120W for 5 minutes, and AE@ZIF-8 solution and PEG-PLGA solution were mixed at a ratio of 7:3, and magnetically stirring at room temperature for 4 min at 250 rpm. Obtaining AE@ZIF-8/PEG-PLGA solution, centrifuging, separating the core for 10 minutes at 12000rpm, and re-suspending and washing twice with methanol to obtain 7ml AE@ZIF-8/PEG-PLGA suspension.
AE@ZIF-8/PEG-PLGA suspension was added dropwise to 1mg/ml of 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC), 1mg/ml of N-hydroxysuccinimide (NHS) each 250. Mu.L, and magnetically stirred at room temperature for 4 hours, 250 revolutions per minute. 1mg/ml transferrin aqueous solution was added dropwise, stirring was continued for 2 hours in the dark, and left standing overnight at 4 ℃.12000 rpm/separating heart for 10 min, collecting precipitate to obtain final product AE@ZIF-8/Tf-PEG-PLGA, re-suspending with methanol, and repeating twice for 12000 rpm/separating heart for 10 min. Resuspension with 75% ethanol, soaking for 30 min, centrifuging, and washing the precipitate twice with physiological saline containing 1% poloxamer.
Experimental example 1, performance measurement
The performance of the drug-loaded ZIF-8 nanoparticles coated with the TF-PEG-PLGA coating prepared in the example 1 and the example 2 is measured, and the structure of a nanoparticle transmission electron microscope, the particle size of the nanoparticles and the zeta potential of the surfaces of the nanoparticles are measured;
the appearance diagram of the nanoparticle transmission electron microscope is shown in fig. 3, which shows that ZIF-8, AE@ZIF-8 and the like are successfully prepared, and the TF-PEG-PLGA coating is successfully attached to the surface of the nanoparticle.
The particle size diagram of the nanoparticles is shown in fig. 4, which shows that the prepared nanoparticles have uniform particle size and can be used for intracranial drug delivery.
The zeta potential diagram of the surface of the nanoparticle is shown in figure 5, which shows that the prepared nanoparticle is weak negative charge and is beneficial to transportation across the blood brain barrier.
The ultraviolet absorption spectrum of the nanoparticle is shown in FIG. 6, and according to the formed AE ultraviolet absorption peak (255 nm), the AE is successfully encapsulated in ZIF-8 and TF-PEG-PLGA/ZIF-8 nanoparticles.
The release performance of the nanoparticle tumor microenvironment is shown in fig. 7, and the nanoparticle is released in the tumor pH microenvironment (ph=5.5) and remains stable in the neutral environment.
The schematic diagram of the blood brain barrier penetrability and tumor targeting of the nanoparticles is shown in fig. 8, compared with the blank drug group, the nanoparticles have higher intracranial distribution and can be enriched in tumor tissues, which indicates that the nanoparticles have the blood brain barrier penetrability and tumor targeting capability.
Finally, it is also noted that the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
While preferred embodiments of the present invention have been described, additional variations and modifications in those embodiments may occur to those skilled in the art once they learn of the basic inventive concepts. It is therefore intended that the following claims be interpreted as including the preferred embodiments and all such alterations and modifications as fall within the scope of the invention.
It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention also include such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.

Claims (7)

1. A method for preparing drug-loaded ZIF-8 nanoparticles coated with TF-PEG-PLGA for targeted delivery of craniocerebral tumors, comprising:
adding a target drug, 2-methylimidazole and zinc nitrate into a methanol solution, mixing, performing a first reaction, purifying, and re-suspending in methanol to obtain a drug-loaded ZIF-8 nanoparticle solution; the mass ratio of the target drug to the 2-methylimidazole to the zinc nitrate is 1: (15-17): (7-8), wherein the target drug is aloe-emodin;
the following operation a or operation B is then performed:
operation a:
the preparation method comprises the steps of (1) activating COOH-PEG-PLGA, uniformly mixing the activated COOH-PEG-PLGA with transferrin in PBS for a second reaction, purifying and re-suspending the activated COOH-PEG-PLGA in PBS to obtain a transferrin modified PEG-PLGA solution, namely TF-PEG-PLGA;
uniformly mixing the drug-carrying ZIF-8 nanoparticle solution and the transferrin modified PEG-PLGA solution to obtain drug-carrying ZIF-8 nanoparticles covered with a TF-PEG-PLGA coating, namely ZIF-8/TF-PEG-PLGA;
or operation B:
uniformly mixing the drug-carrying ZIF-8 nanoparticle solution with COOH-PEG-PLGA phosphate buffer solution, and purifying and re-suspending in methanol to obtain a drug-carrying @ ZIF-8/PEG-PLGA suspension;
activating the drug-carrying @ ZIF-8/PEG-PLGA suspension, mixing with transferrin, purifying, and re-suspending in methanol to obtain drug-carrying ZIF-8 nanoparticles covered with TF-PEG-PLGA coating, namely ZIF-8/TF-PEG-PLGA;
in the operation A, the volume ratio of the drug-carrying ZIF-8 nanoparticle solution to the transferrin modified PEG-PLGA solution is (6-8): (2-4); in the operation B, the volume ratio of the drug-carrying ZIF-8 nanoparticle solution to the COOH-PEG-PLGA phosphate buffer solution is (6-8): (2-4).
2. The method of preparing drug-loaded ZIF-8 nanoparticles coated with TF-PEG-PLGA for targeted delivery of craniocerebral tumors of claim 1, wherein the conditions of the first and second reactions each comprise: magnetic stirring is carried out at the rotating speed of 200-300 rpm, the reaction is carried out at the room temperature of 0.5-2 h, and then the mixture is kept stand.
3. The method for preparing drug-loaded ZIF-8 nanoparticles coated with TF-PEG-PLGA for targeted delivery of craniocerebral tumors of claim 1, wherein the method for COOH-PEG-PLGA activation comprises: the COOH-PEG-PLGA is activated by adopting 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) to activate carboxyl groups on the COOH-PEG-PLGA.
4. The method for preparing drug-loaded ZIF-8 nanoparticles coated with TF-PEG-PLGA for targeted delivery of craniocerebral tumors according to claim 1, wherein the mass ratio of transferrin to COOH-PEG-PLGA in operation a and in operation B is 1: (700-800).
5. The method of preparing drug-loaded ZIF-8 nanoparticles coated with TF-PEG-PLGA for targeted delivery of craniocerebral tumors of claim 1, further comprising:
and (3) carrying out centrifugal purification, sterilization and washing on the drug-loaded ZIF-8 nano particles covered with the TF-PEG-PLGA coating in the presence of a surfactant.
6. A drug-loaded ZIF-8 nanoparticle covering a TF-PEG-PLGA coating for targeted delivery of craniocerebral tumors, prepared by the method of any one of claims 1 to 5, wherein the nanoparticle has a core-shell structure:
the nuclear layer is ZIF-8 nanoparticles carrying medicine;
and the shell layer is wrapped on the periphery of the core layer, and the shell layer is transferrin modified PEG-PLGA.
7. Use of the drug-loaded ZIF-8 nanoparticles coated with TF-PEG-PLGA coating for targeted delivery of craniocerebral tumors according to claim 6 for the preparation of drug-loaded nanoparticle drugs for targeted delivery of craniocerebral tumors.
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