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Specific target polypeptide self-assembled nano-carrier, drug-carrying nanoparticle and preparation method

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

Active Publication Date: 2017-06-13
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 target polypeptide self-assembled nano-carrier, drug-carrying nanoparticle and preparation method
  • Specific target polypeptide self-assembled nano-carrier, drug-carrying nanoparticle and preparation method
  • Specific target polypeptide self-assembled nano-carrier, drug-carrying nanoparticle and preparation method

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preparation example Construction

[0042] Wherein, the targeting peptide that can be recognized by the epidermal growth factor receptor at the tumor site is a peptide segment known in the art and can be purchased commercially. Alternatively, it can be prepared by Fmoc solid-phase synthesis known in the art. The present invention provides a specific preparation method. Those skilled in the art can understand that the method is not intended to limit the present invention. The raw materials involved in the following preparation method are commercially available, for example purchased from Jill 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 make it fully swell, and finally discharge the solvent N,N-dimethylformamide base formamide.

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

Embodiment 1

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

[0050] (1) Preparation of amphiphilic polypeptide molecules: take 50 mg of the 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 Catalyst diisopropylethylamine (DIEA), reacted at room temperature for 12 hours. After stopping the reaction, the liquid was added dropwise into anhydrous ether, and a white precipitate appeared immediately. Centrifuge (rotating speed: 5000rpm, centrifuge 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: Dissolve amphiphilic polypeptide molecules in 20 uL of dimethyl sulfoxide solution at room temperature, disperse them in 1 mL of aqueous solution under ultras...

Embodiment 2

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

[0054] (1) Preparation of amphiphilic polypeptide molecules: take 50 mg of the 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 Catalyst diisopropylethylamine (DIEA), reacted at room temperature for 12 hours. After stopping the reaction, the liquid was added dropwise into anhydrous ether, and a white precipitate appeared immediately. Centrifuge (5000 rpm, centrifugation time 5 min) 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, which is named P-2.

[0055] (2) Preparation of drug-loaded nanoparticles: at room temperature, according to the molar ratio of the drug to the amphiphilic polypeptide molecule being 1: (5-20), 1 mg ...

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Abstract

The invention relates to the technical field of biology and in particular relates to a specific target polypeptide self-assembled nanoparticle. The nanoparticle is prepared from a hydrophobic anti-tumor drug with a therapeutic dosage and an amphipathic polypeptide which covers the periphery of the hydrophobic anti-tumor drug through a self-assembling manner, wherein the amphipathic polypeptide is a target peptide which can be used for specifically targeting a epidermal growth factor receptor of a tumor cell; a terminal N of the target peptide is coupled with a hydrophobic functional molecule. After the nanoparticle targets the tumor cell, the target peptide is exposed; the nanoparticle targets the tumor cell and enters the tumor cell through receptor-mediated endocytosis, and the drug is released to inhibit DNA (Deoxyribonucleic Acid) synthesis and repairing; the nanoparticle has dual killing effects on the tumor cells and the growth of the tumor cell is inhibited. The amphipathic polypeptide does not generate a covalent bond in a self-assembling process and no reverse reaction is caused; the specific target polypeptide self-assembled nanoparticle is used for treating tumors and has the advantages of no toxin and good biocompatibility.

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, as well as their preparation method. Background technique [0002] The self-assembly process is a common phenomenon in the evolution process of hundreds of millions of years 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 macromolecular systems with biological functions are formed through molecular self-assembly, and even more complete and complex living organisms are also products of self-assembly. The fundamental driving force for the self-assembly process is the weak intermolecular interactions, mainly non-covalent bonds. The synergistic effect of these non-covalent bonds such as hydrogen bonds, van der Waals forces, electrostatic...

Claims

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Application Information

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Patent Type & Authority Applications(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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