CN113577279A - Cell membrane coated functionalized black phosphorus nano-composite, preparation method and application - Google Patents

Cell membrane coated functionalized black phosphorus nano-composite, preparation method and application Download PDF

Info

Publication number
CN113577279A
CN113577279A CN202110953460.6A CN202110953460A CN113577279A CN 113577279 A CN113577279 A CN 113577279A CN 202110953460 A CN202110953460 A CN 202110953460A CN 113577279 A CN113577279 A CN 113577279A
Authority
CN
China
Prior art keywords
black phosphorus
cell membrane
bpag
nano
functionalized
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202110953460.6A
Other languages
Chinese (zh)
Inventor
乔海石
杨立新
叶优清
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
China Pharmaceutical University
Original Assignee
China Pharmaceutical University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by China Pharmaceutical University filed Critical China Pharmaceutical University
Priority to CN202110953460.6A priority Critical patent/CN113577279A/en
Publication of CN113577279A publication Critical patent/CN113577279A/en
Pending legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/44—Oxidoreductases (1)
    • A61K38/443—Oxidoreductases (1) acting on CH-OH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/545—Heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y40/00—Manufacture or treatment of nanostructures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y101/00—Oxidoreductases acting on the CH-OH group of donors (1.1)
    • C12Y101/03—Oxidoreductases acting on the CH-OH group of donors (1.1) with a oxygen as acceptor (1.1.3)
    • C12Y101/03004—Glucose oxidase (1.1.3.4)

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nanotechnology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Physics & Mathematics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Physics & Mathematics (AREA)
  • Manufacturing & Machinery (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Botany (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses a cell membrane coated functionalized black phosphorus nano-composite, a preparation method and application thereof; the functionalized black phosphorus nano-composite consists of a coated cell membrane and black phosphorus oxidized on the surface and combined with functional molecules, an oxidation product PxOy formed after the surface of the black phosphorus is primarily oxidized is beneficial to the bonding and loading of the functional molecules, and the photothermal effect is combined to promote the release of drug molecules and biological cascade reaction, so that the purpose of tumor and postoperative cooperative treatment is achieved; meanwhile, the coating of the cell membrane is combined to provide the targeting capability of organs and tumors, the stability of the nano compound in blood circulation is improved, the infiltration of the compound in target tissues is increased, and a more excellent treatment effect is exerted; the nano-composite prepared by the method has good stability, is easy to prepare in large scale, and shows excellent treatment effect in preparation of tumor-targeted drugs and postoperative cooperative treatment.

Description

Cell membrane coated functionalized black phosphorus nano-composite, preparation method and application
Technical Field
The invention relates to a black phosphorus nano-composite, in particular to a functional black phosphorus nano-composite coated by a cell membrane, and also comprises a preparation method and application of the composite.
Background
Tumors are one of the most fatal and common diseases at present, and the traditional tumor treatment methods mainly comprise surgical resection, radiotherapy, chemotherapy and the like. However, a single tumor treatment strategy is difficult to effectively remove tumor cells, and chemotherapy drugs lack selectivity and easily cause toxic and side effects, and high tumor heterogeneity easily causes problems of multidrug resistance and the like, so that patients still face risks of postoperative metastasis and relapse despite active surgical treatment and radiotherapy and chemotherapy. In view of the difficulty in completely eradicating tumors in the conventional treatment methods, the search for a multi-mode and multifunctional tumor cooperative treatment method is an urgent problem to be solved in the current anti-tumor research.
Due to good biocompatibility, excellent photothermal conversion performance and conversion efficiency, the black phosphorus attracts great attention in the field of tumor treatment, and photothermal therapy (PTT) is proved to be capable of effectively activating tumor immune microenvironment. Therefore, the combination of multiple treatment modes is realized by utilizing the advantages of the photo-thermal property of the black phosphorus, the bonding and loading capacity of functional drug molecules endowed with the black phosphorus after oxidation and the like, and the tumor of the cell membrane and the postoperative targeting are combined, so that the cooperative treatment of the tumor and the inhibition of postoperative recurrence are achieved.
Disclosure of Invention
The purpose of the invention is as follows: aiming at the defects of single treatment and simple combined treatment in the prior art, the invention realizes the synergistic effect of a plurality of treatment modes, provides a functional black phosphorus nano compound coated by cell membranes, and also provides a preparation method and application of the functional black phosphorus compound.
The technical scheme is as follows: the functional black phosphorus nano composite coated by the cell membrane comprises the cell membrane, the black phosphorus and functional molecules, and the nano composite is in a core-shell structure, wherein the shell layer is the cell membrane, and the core layer is the black phosphorus combined with the functional molecules.
Preferably, the cell membrane is a macrophage membrane, neutrophil membrane, surface-functionalized macrophage membrane or surface-functionalized neutrophil membrane.
Preferably, the functional molecule comprises amino acids carboxyl-containing small molecules, carboxyl-containing linker, functional protein such as glucose oxidase (GOx), and superoxide dismutase.
Preferably, the amino acid carboxyl-containing small molecule is arginine, proline or glycine; the linker containing carboxyl is glyceric acid, phenylboronic acid or cis-aconitic anhydride; the protein is glucose oxidase (GOx) or catalase.
The preparation method of the cell membrane coated functionalized black phosphorus nano-composite comprises the following steps:
(1) preparation of black phosphorus-arginine complex (BPA): taking 4-Dimethylaminopyridine (DMAP), Black Phosphorus (BP) and L-arginine, reacting in a mixed solution of an organic solvent and water, removing unreacted L-arginine, and separating to obtain BPA;
(2) preparation of black phosphorus-arginine-glucose oxidase (BPAG): taking 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC), N-hydroxysuccinimide (NHS) and glucose oxidase (GOx) to react in water; adding the BPA prepared in the step (1), reacting, and separating to obtain BPAG;
(3) preparation of cell membrane: removing cultured cells, washing with PBS, digesting with pancreatin, collecting digested cells, centrifuging for 500g 4min, washing with PBS, adding cell lysis buffer solution, homogenizing, centrifuging, collecting supernatant, centrifuging, collecting precipitate, and freeze drying the precipitate to obtain purified cell membrane;
(4) preparation of cell membrane-coated functionalized black phosphorus nanocomplex (M @ BPAG): firstly, dissolving a proper amount of BPAG (BPAG) in PBS (phosphate buffer solution), dissolving a certain amount of cell membranes in a mixed solution of ethanol and PBS, carrying out mixed water bath ultrasound on the cell membranes and the mixed solution, then taking a proper amount of PBS, and assembling by using a nano precipitation method to obtain the cell membrane coated functionalized black phosphorus nano compound.
Preferably, in the step (1), the molar ratio of the 4-Dimethylaminopyridine (DMAP), the Black Phosphorus (BP) and the L-arginine is 1: 1: 5-10; the organic solvent is N, N' -Dimethylformamide (DMF).
Preferably, in the step (2), the molar ratio of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC), N-hydroxysuccinimide (NHS) and glucose oxidase (GOx) is 2: 1: 4 to 8.
Preferably, in the step (4), the molar ratio of the cell membrane to the BPAG is 10-20: 1.
the invention also discloses application of the cell membrane coated functionalized black phosphorus nano-composite, and the functionalized black phosphorus nano-composite can be applied to preparation of tumor targeted drugs and postoperative cooperative therapy drugs.
The invention principle is as follows: according to the invention, through mild chemical reaction, on one hand, an oxidation product PxOy formed after the surface of Black Phosphorus (BP) is primarily oxidized endows the Black Phosphorus (BP) with a functional modification characteristic, the bonding and the loading of functional molecules are facilitated, the photothermal action of the BP promotes GOx to catalyze glucose to generate hydrogen peroxide, and the hydrogen peroxide further promotes arginine to release NO under the action of temperature rise and thus initiates a series of biological cascade reactions. The photo-thermal effect of the black phosphorus protected by the modification method realizes the purpose of tumor and postoperative cooperative treatment. On the other hand, the coating of the cell membrane and the cell membrane after functional modification enables the functionalized black phosphorus nano-composite to have the targeting capability of organs and tumors, improves the stability of the nano-composite in blood circulation, increases infiltration in target tissues and also endows the composite with the capability of further modifying other functional molecules on the surface of the cell membrane. In conclusion, the nano-composite prepared by the method has good stability, is easy to prepare in large quantity, shows excellent treatment effect in vivo of in-situ tumor-bearing mice, and further provides a new way and strategy for tumor and postoperative treatment.
Has the advantages that: compared with the prior art, the invention has the following remarkable advantages:
(1) the functionalized black phosphorus nano-composite coated by the cell membrane has the advantages of good photo-thermal effect, outstanding stability and biological cascade release:
(2) the preparation method of the cell membrane coated functionalized black phosphorus nano-composite has the advantages of mild reaction conditions, high yield and large-scale preparation of depression.
(3) In the aspect of preparing tumor-targeted drugs and postoperative cooperative therapy drugs, the functionalized black phosphorus nanocomposite disclosed by the invention has the advantages of good targeting performance and remarkable treatment effect, and animal experiment results show that the coating of cell membranes and the exertion of biological cascade reaction effects enable the tumor inhibition effect of the M @ BPAG group to be remarkably higher than that of other groups, and the M @ BPAG group can remarkably inhibit the recurrence of tumors from postoperative model results.
Drawings
FIG. 1 is a TEM spectrum and a particle size spectrum of black phosphorus;
FIG. 2 is a TEM and particle size spectrum of BPA;
FIG. 3 is a TEM and particle size spectrum of BPAG;
FIG. 4 is a TEM and particle size spectrum of M @ BPAG;
FIG. 5 is a potential map of BP, BPA, BPAG, M @ BPAG;
FIG. 6 shows BPAG at the same irradiation time H202A release profile;
FIG. 7 shows the H of BPAG under different irradiation times202A release profile;
FIG. 8 is a graph showing the therapeutic effect of glioma-bearing mice;
FIG. 9 is a graph of fluorescence magnitude data for various groups of tumors after animal treatment.
FIG. 10 is a graph showing the effect of the post-operation treatment of glioma-bearing mice;
Detailed Description
The technical scheme of the invention is further explained by combining the attached drawings.
Example 1
(1) Synthesis of BPA: 10mg of black phosphorus was dispersed in 2mL of DMF, and 100mg of L-arginine and 10mg of DMAP were added. The mixture was reacted for 8h with magnetic stirring at 30 ℃. After completion of the reaction, the reaction solution was dialyzed for 6 hours to remove unreacted arginine. After dialysis, the mixture was centrifuged at 17000 Xg for 4min and washed three times with deionized water, and the final product was stored at 4 ℃.
(2) Synthesis of BPAG: 1mg GOx was dissolved in 5mL deionized water, 25mg EDC and 50mg NHS were slowly added dropwise, and after stirring the reaction at room temperature for 1h, 10mg BPA was added to the mixture. The reaction solution was subjected to a reaction in an oil bath at 30 ℃ and then dialyzed to remove unreacted GOx. After dialysis, the mixture was centrifuged at 17000 Xg for 4min and washed three times with deionized water, and the final product was stored at 4 ℃.
(3) Synthesis of M @ BPAG: 1mg of cell membrane was redissolved in 1ml of PBS by vortexing. 1mg of BPAG was dispersed into 1mL of PBS using water bath sonication. Slowly dripping the cell membrane solution into 100 mu L of BPAG solution under the ultrasonic condition, and carrying out ultrasonic treatment for 5min to obtain M @ BPAG.
Example 2
(1) Synthesis of BPA: 105mg of black phosphorus was dispersed in 2mL of DMF, and 100mg of L-arginine and 15mg of DMAP were added. The mixture was reacted for 8h with magnetic stirring at 30 ℃. After completion of the reaction, the reaction solution was dialyzed for 6 hours to remove unreacted arginine. After dialysis, the mixture was centrifuged at 17000 Xg for 4min and washed three times with deionized water, and the final product was stored at 4 ℃.
(2) Synthesis of BPAG: 1.5mg GOx was dissolved in 5mL deionized water, 38mg EDC and 75mg NHS were slowly added dropwise, and after stirring the reaction at room temperature for 1h, 15mg BPA was added to the mixture. The reaction solution was subjected to a reaction in an oil bath at 30 ℃ and then dialyzed to remove unreacted GOx. After dialysis, the mixture was centrifuged at 17000 Xg for 4min and washed three times with deionized water, and the final product was stored at 4 ℃.
(3) Synthesis of M @ BPAG: 2mg of cell membrane were redissolved in 1ml PBS by vortexing. 1mg of BPAG was dispersed into 1mL of PBS using water bath sonication. Slowly dripping the cell membrane solution into 100 mu L of BPAG solution under the ultrasonic condition, and carrying out ultrasonic treatment for 5min to obtain M @ BPAG.
Example 3
Characterization and Synthesis of M @ BPAG
(1) Synthesis of BPA: 20mg of black phosphorus was dispersed in 2ml of DMF, and 100mg of L-arginine and 20mg of DMAP were added. The mixture was reacted for 8h with magnetic stirring at 30 ℃. After completion of the reaction, the reaction solution was dialyzed for 6 hours to remove unreacted arginine. After dialysis, the mixture was centrifuged at 17000 Xg for 4min and washed three times with deionized water, and the final product was stored at 4 ℃.
(2) Synthesis of BPAG: 2mgGOx dissolved in 5mL deionized water, slowly adding dropwise 50mgEDC and 100mgNHS, room temperature stirring reaction for 1h, then to the mixture added 10 mgBPA. The reaction solution was subjected to a reaction in an oil bath at 30 ℃ and then dialyzed to remove unreacted GOx. After dialysis, the mixture was centrifuged at 17000 Xg for 4min and washed three times with deionized water, and the final product was stored at 4 ℃.
(3) Synthesis of M @ BPAG: 2mg of cell membrane were redissolved in 1ml PBS by vortexing. 1mg BPAG was dispersed into 1mLPBS using water bath sonication. Slowly dripping the cell membrane solution into 100 mu L of BPAG solution under the ultrasonic condition, and carrying out ultrasonic treatment for 5min to obtain M @ BPAG.
Measuring a particle size map and a potential: the hydrodynamic diameter of each of the appropriate amounts of black phosphorus, BPA, BPAG, M @ BPAG was determined in PB 7.4. As is clear from the results of FIGS. 1 to 4, the particle size of BP was about 77nm, that of BPA was about 118nm, that of BPAG was about 119nm, and that of M @ BPAG was about 134 nm. As can be seen from FIG. 5, the potential of BP is about-20 mv, the potential of BPA is about 10mv, the potential of BPAG is about-1.5 mv, and the potential of M @ BPAG is about-9.8 mv.
H2O2Generated assay
M @ BPAG prepared in each example was dissolved in a glucose solution and irradiated with near infrared light (wavelength 808nm) to promote oxidation of glucose by GOx and release H2O2。
H2O2The resulting assay: a certain amount of BPAG was taken and H under near infrared light irradiation was measured in a PBS solution containing 1mg/mL of glucose2O2The amount produced. The experiment was divided into two groups, one group was irradiated with 1mg/mL of BPAG solution in 1mg/mL of glucose in PBS for 0, 1, 3, 5, 7, 10min, and the other group was irradiated with 1mg/mL of glucose in PBS for 10 min. As shown in the attached figures 6-7, H can be significantly promoted by near-infrared irradiation for 1min2O2Generation of (A), H2O2Can lead to better tumor killing effect.
Example 4
Evaluation of nano-reactor combination therapy for brain glioma
The in vivo anti-tumor effect of brain glioma was evaluated using GL261-Luc tumor-bearing mice. After establishment of orthotopic gliomas, mice were randomly divided into 5 groups according to the above example to verify the treatment effect of each group on tumors, PBS, M @ BPA (4mg kg)-1Calculated as BP), M @ BPA + NIR, M @ BPAG (6mg kg)-1Calculated as BP), M @ BPAG + NIR. Each group of tumor-bearing mice was injected 100. mu.L into the tail vein. 8 hours after injection, near-infrared laser (0.8W/cm)2) Tumors were irradiated for 20 min. Bioluminescence intensity of tumor-bearing mice was imaged using the IVIS instrument every 3 days after injection of d-fluorescein potassium salt to determine tumor growth. As can be seen from FIG. 8, PBS, M @ BPA and M @ BPA + NIR did not inhibit tumor growth. The results for the M @ BPAG and M @ BPAG + NIR groups showed that both the M @ BPAG and M @ BPAG + NIR groups achieved tumor inhibition. Further comparison of the results of the ROI values of the groups shows that the growth trend of the tumors of the groups is consistent with the results of FIG. 8, as can be seen from the results of FIG. 9.
Example 5
Evaluation of brain glioma after nano-reactor combination therapy
GL261-Luc tumor-bearing mice were used to evaluate the in vivo anti-tumor effect of the postoperative glioma model. After the establishment of orthotopic glioma, 5 days after tumor growth, mice were randomly divided into 3 groups according to the above examples to verify the treatment effect of each group on tumor, PBS and BPAG (6mg kg)-1Calculated as BP), M @ BPAG. After the groups are divided, the brain glioma of each group of mice is cleaned, and 100 mu L of the mouse tail is injected into the vein of each group of mice after the next day. 8 hours after injection, near-infrared laser (0.8W/cm)2) Tumors were irradiated for 20 min. Bioluminescence intensity of tumor-bearing mice was imaged using the IVIS instrument every 3 days after injection of d-fluorescein potassium salt to determine tumor growth. As shown in FIG. 10, the PBS and BPAG groups still had tumor recurrence after the postoperative surgery, and the M @ BPAG group could achieve the effect on the tumor recurrence after the postoperative surgeryAnd (4) inhibiting.

Claims (9)

1. The cell membrane-coated functionalized black phosphorus nano-composite is characterized by comprising a cell membrane, black phosphorus and functional molecules, wherein the nano-composite is in a core-shell structure, a shell layer is the cell membrane, and a core layer is the black phosphorus combined with the functional molecules.
2. The functionalized black phosphorus nanocomposite according to claim 1, wherein the cell membrane is a macrophage membrane, a neutrophil membrane, a surface functionalized macrophage membrane or a surface functionalized neutrophil membrane.
3. The functionalized black phosphorus nanocomposite of claim 1, wherein the functional molecule comprises an amino acid carboxyl-containing small molecule, a carboxyl-containing linker, or a functional protein.
4. The functionalized black phosphorus nanocomposite of claim 3, wherein the amino acid carboxyl group-containing small molecule is arginine, proline or glycine; the linker containing carboxyl is glyceric acid, phenylboronic acid or cis-aconitic anhydride; the functional protein is glucose oxidase (GOx) or catalase.
5. A method for preparing the cell membrane coated functionalized black phosphorus nano-composite of claim 1, comprising the following steps:
(1) preparation of black phosphorus-arginine complex (BPA): taking 4-Dimethylaminopyridine (DMAP), Black Phosphorus (BP) and L-arginine, reacting in a mixed solution of an organic solvent and water, removing unreacted L-arginine, and separating to obtain BPA;
(2) preparation of black phosphorus-arginine-glucose oxidase (BPAG): taking 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC), N-hydroxysuccinimide (NHS) and glucose oxidase (GOx) to react in water; adding the BPA prepared in the step (1), reacting, and separating to obtain BPAG;
(3) preparation of cell membrane: removing cultured cells, washing with PBS, digesting with pancreatin, collecting digested cells, centrifuging, washing with PBS, adding cell lysis buffer solution, homogenizing, centrifuging, collecting supernatant, centrifuging, collecting precipitate, and freeze drying the precipitate to obtain purified cell membrane;
(4) preparation of cell membrane-coated functionalized black phosphorus nanocomplex (M @ BPAG): and (3) dissolving BPAG in PBS, dissolving the cell membrane obtained in the step (3) in a mixed solution of ethanol and PBS, performing ultrasonic treatment on the cell membrane and the cell membrane in a mixed water bath, then taking a proper amount of PBS, and assembling by using a nano precipitation method to obtain the cell membrane coated functionalized black phosphorus nano compound.
6. The method of claim 5, wherein in step (1), the molar ratio of 4-Dimethylaminopyridine (DMAP), Black Phosphorus (BP) and L-arginine is 1: 1: 5-10; the organic solvent is N, N' -Dimethylformamide (DMF).
7. The method according to claim 5, wherein in the step (2), the molar ratio of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC), N-hydroxysuccinimide (NHS) and glucose oxidase (GOx) is 2: 1: 4 to 8.
8. The method according to claim 5, wherein in the step (4), the molar ratio of the cell membrane to BPAG is 10 to 20: 1.
9. the use of the cell membrane-coated functionalized black phosphorus nanocomposite of claim 1, wherein the functionalized black phosphorus nanocomposite can be used for preparing a tumor-targeted drug and a drug for postoperative synergistic treatment.
CN202110953460.6A 2021-08-19 2021-08-19 Cell membrane coated functionalized black phosphorus nano-composite, preparation method and application Pending CN113577279A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110953460.6A CN113577279A (en) 2021-08-19 2021-08-19 Cell membrane coated functionalized black phosphorus nano-composite, preparation method and application

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110953460.6A CN113577279A (en) 2021-08-19 2021-08-19 Cell membrane coated functionalized black phosphorus nano-composite, preparation method and application

Publications (1)

Publication Number Publication Date
CN113577279A true CN113577279A (en) 2021-11-02

Family

ID=78238381

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110953460.6A Pending CN113577279A (en) 2021-08-19 2021-08-19 Cell membrane coated functionalized black phosphorus nano-composite, preparation method and application

Country Status (1)

Country Link
CN (1) CN113577279A (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110974978A (en) * 2019-12-23 2020-04-10 暨南大学 Nano-catalyst for treating tumor and preparation method and application thereof
CN111686251A (en) * 2020-06-17 2020-09-22 福建医科大学孟超肝胆医院(福州市传染病医院) Bionic nano material for acoustic power/gas synergistic anti-tumor therapy and preparation method thereof
CN111870693A (en) * 2020-08-12 2020-11-03 中国药科大学 Method for promoting arginine to rapidly release NO by black phosphorus

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110974978A (en) * 2019-12-23 2020-04-10 暨南大学 Nano-catalyst for treating tumor and preparation method and application thereof
CN111686251A (en) * 2020-06-17 2020-09-22 福建医科大学孟超肝胆医院(福州市传染病医院) Bionic nano material for acoustic power/gas synergistic anti-tumor therapy and preparation method thereof
CN111870693A (en) * 2020-08-12 2020-11-03 中国药科大学 Method for promoting arginine to rapidly release NO by black phosphorus

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
WENQUAN OU ET AL: ""Tailored Black Phosphorus for Erythrocyte Membrane Nanocloaking with Interleukin-1α siRNA and Paclitaxel for Targeted, Durable, and Mild Combination Cancer Therapy"", 《THERANOSTICS》 *
XUEYUAN HUANG ET AL: ""Anti-tumour effects of red blood cell membranecamouflaged black phosphorous quantum dots combined with chemotherapy and antiinflammatory therapy"", 《ARTIFICIAL CELLS, NANOMEDICINE, AND BIOTECHNOLOGY》 *
官启潇 等: ""细胞膜修饰的纳米载体与肿瘤免疫治疗"", 《化学进展》 *

Similar Documents

Publication Publication Date Title
Pan et al. A cancer cell membrane-encapsulated MnO 2 nanoreactor for combined photodynamic-starvation therapy
Liang et al. Core-shell structured upconversion nanocrystal-dendrimer composite as a carrier for mitochondria targeting and catalase enhanced anti-cancer photodynamic therapy
Zhao et al. Self-assembled nanomaterials for enhanced phototherapy of cancer
Mu et al. Engineering of nanoscale coordination polymers with biomolecules for advanced applications
Li et al. Protein shell-encapsulated Pt clusters as continuous O2-supplied biocoats for photodynamic therapy in hypoxic cancer cells
CN110974978A (en) Nano-catalyst for treating tumor and preparation method and application thereof
CN109432439B (en) Metal-porphyrin nanoparticle with sonodynamic treatment effect, preparation method and application thereof
Yao et al. Application of organic frame materials in cancer therapy through regulation of tumor microenvironment
Han et al. Supramolecular nanozyme-based cancer catalytic therapy
CN111558032B (en) Protein nano-drug and preparation method and application thereof
CN108210506B (en) pH response and polypeptide targeting nano-drug delivery carrier and preparation and application thereof
CN107242996B (en) A kind of gel rubber material and preparation method thereof for oncotherapy
CN105641710B (en) The targeted oxidative graphene of HA/RGD modification is double to carry medicine composite material and preparation method thereof
Zhu et al. Sonodynamic cancer therapy by novel iridium-gold nanoassemblies
Xiao et al. Recent research progress in the construction of active free radical nanoreactors and their applications in photodynamic therapy
Zhu et al. Novel design of multifunctional nanozymes based on tumor microenvironment for diagnosis and therapy
CN108524946A (en) Ternary complex Nano medication and preparation method thereof and the application in preparing light controlled release nanometer delivery system
Wang et al. Trace-Water-Induced Competitive Coordination Synthesis and Functionalization of Porphyrinic Metal–Organic Framework Nanoparticles for Treatment of Hypoxic Tumors
Huang et al. A hierarchical supramolecular nanozyme platform for programming tumor-specific PDT and catalytic therapy
Chu et al. Manganese amplifies photoinduced ROS in toluidine blue carbon dots to boost MRI guided chemo/photodynamic therapy
Kang et al. Applications of nanocomposites based on zeolitic imidazolate framework-8 in photodynamic and synergistic anti-tumor therapy
CN110917349B (en) Bowl-shaped ISP (internet service provider) composite functional nano particle as well as preparation method and application thereof
CN111040180B (en) Biological cascade reaction type photodynamic integrated biopolymer and preparation method and application thereof
CN113577279A (en) Cell membrane coated functionalized black phosphorus nano-composite, preparation method and application
Meng et al. Self-assembled nanoplatforms for chemodynamic therapy

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20211102