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Specific targeting polypeptide self-assembled nanocarrier, drug-loaded nanoparticle and preparation method

A technology targeting peptides and nano-carriers, which is applied in pharmaceutical formulations, drug combinations, anti-tumor drugs, etc., can solve the problems of accumulated toxicity and achieve the effects of small side effects, good drug development potential, and good biocompatibility

Active Publication Date: 2022-08-09
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Synthetic materials can build self-assembled nanostructures, but long-term use accumulates potential toxicity

Method used

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  • Specific targeting polypeptide self-assembled nanocarrier, drug-loaded nanoparticle and preparation method
  • Specific targeting polypeptide self-assembled nanocarrier, drug-loaded nanoparticle and preparation method
  • Specific targeting polypeptide self-assembled nanocarrier, drug-loaded nanoparticle and preparation method

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preparation example Construction

[0042] Among them, the targeting peptide that can be recognized by epidermal growth factor receptor at the tumor site is a peptide segment known in the art and can be obtained commercially. Alternatively, it can be prepared by solid-phase synthesis of Fmoc known in the art. The present invention provides a specific preparation method, and those skilled in the art can understand that this method is not used to limit the present invention, and the raw materials involved in the following preparation methods are commercially available, such as those from Gill Biochemical (Shanghai) Co., Ltd., Sigma-Aldrich Corporation.

[0043] (1) Take 1.01 g of dichlorotrityl chloride resin to the peptide synthesis device, add dry N,N-dimethylformamide to soak the resin for half an hour to fully swell it, and finally discharge the solvent N,N-dimethylformamide formamide.

[0044] (2) Weigh 0.2 g of Fmoc-Gly-OH and dissolve it with 5 ml of N,N-dimethylformamide, then transfer the solution to th...

Embodiment 1

[0049] A preparation method of a specific targeting polypeptide self-assembled nanocarrier, comprising the following steps:

[0050] (1) Preparation of amphiphilic polypeptide molecule: take 50 mg of targeting peptide P-1 prepared by the above method, dissolve it in 5 mL of N,N-dimethylformamide solution, add 350 mg of octadecanoic acid, 2 mL of The catalyst is diisopropylethylamine (DIEA), and the reaction is carried out at room temperature for 12 hours. After the reaction was stopped, the liquid was added dropwise to anhydrous ether, and a white precipitate appeared immediately. Centrifuge (rotation speed is 5000rpm, centrifugation time 5min) to separate the above suspension to remove the supernatant, freeze-dry the obtained product, and collect the white powder to obtain the amphiphilic polypeptide molecule.

[0051] (2) Preparation of nanocarriers: at room temperature, the amphiphilic polypeptide molecule was dissolved in 20uL of dimethyl sulfoxide solution, dispersed in ...

Embodiment 2

[0053] A preparation method of self-assembled drug-loaded nanoparticles with specific targeting polypeptide, comprising the following steps:

[0054] (1) Preparation of amphiphilic polypeptide molecule: take 50 mg of targeting peptide P-1 prepared by the above method, dissolve it in 5 mL of N,N-dimethylformamide solution, add 350 mg of octadecanoic acid, 2 mL of The catalyst is diisopropylethylamine (DIEA), and the reaction is carried out at room temperature for 12 hours. After the reaction was stopped, the liquid was added dropwise to anhydrous ether, and a white precipitate appeared immediately. Centrifuge (rotation speed is 5000rpm, centrifugation time 5min) to separate the above suspension to remove the supernatant, freeze-dry the obtained product, and collect the white powder to obtain the amphiphilic polypeptide molecule, named P-2.

[0055] (2) Preparation of drug-loaded nanoparticles: at room temperature, according to the molar ratio of drug and amphiphilic polypeptid...

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Abstract

The present invention relates to the field of biotechnology, in particular to a specific targeting polypeptide self-assembled nanoparticle, the nanoparticle comprises a therapeutic amount of a hydrophobic antitumor drug, and two self-assembly methods wrapped around the hydrophobic antitumor drug. An affinity polypeptide, the amphiphilic polypeptide is a targeting peptide that can specifically target tumor cell epidermal growth factor receptor, and the N-terminus of the targeting peptide is coupled with a hydrophobic functional molecule. After targeting tumor cells, the nanoparticles expose targeting peptides, target tumor cells, enter tumor cells through receptor-mediated endocytosis, release drugs, inhibit DNA synthesis and repair, and perform double killing on tumor cells , inhibit tumor growth. The amphiphilic polypeptide does not generate covalent bonds and has no reverse reaction during the self-assembly process, and has the advantages of non-toxicity and good biocompatibility for tumor treatment.

Description

technical field [0001] The invention belongs to the field of self-assembled nanomaterials, and in particular relates to a specific targeting polypeptide self-assembled nanocarrier and nanoparticle, and a preparation method thereof. Background technique [0002] The self-assembly process is a ubiquitous phenomenon in the billions of years of evolution in nature. Biochemical processes such as DNA synthesis, RNA transcription and regulation, and protein synthesis and folding are all self-assembly processes. In addition, a large number of complex and biologically functional macromolecular systems are formed by molecular self-assembly, and even more complete and complex living organisms are the products formed by self-assembly. The fundamental driving force of the self-assembly process is the weak intermolecular interaction forces, mainly non-covalent bonds. The synergistic effect of these non-covalent bonds, such as hydrogen bonding, van der Waals force, electrostatic force, h...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/51A61K47/42A61K45/00A61K31/502A61K31/7068A61P35/00
CPCA61K45/00A61K9/5169A61K31/502A61K31/7068
Inventor 聂广军赵颖祁迎秋
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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