A peptide nanoparticle capable of lysosome escape and its preparation method and application

A nanoparticle and lysosome technology, which is applied in the field of peptide nanoparticles capable of lysosome escape and its preparation, can solve the problems of limitation and lack of membrane-dissolving peptides, so as to enhance specificity, improve endosomal escape, improve effect of treatment

Active Publication Date: 2022-03-08
LINYI UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Since general targeted drugs do not have membrane-dissolving peptides, the main obstacle is limited by the encapsulation of endoplasmic lysosomes

Method used

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  • A peptide nanoparticle capable of lysosome escape and its preparation method and application
  • A peptide nanoparticle capable of lysosome escape and its preparation method and application
  • A peptide nanoparticle capable of lysosome escape and its preparation method and application

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preparation example Construction

[0034]The present invention provides the preparation method of the peptide nanoparticle, comprising the following steps: 1) self-assembling tryptophan-phenylalanine dipeptide DNPs to form self-assembled DNPs; 2) self-assembled DNPs surface Carboxyl activation to obtain carboxyl activated self-assembled DNPs; 3) Carboxyl activated self-assembled DNPs were mixed with AS1411 aptamer, influenza hemagglutinin peptide HA and clofarabine to obtain DNPs / Clolar / AS1411 / HA; 4) SiRNA was mixed with DNPs / Clolar / AS1411 / HA mixing reaction to obtain DNPs / Clolar / AS1411 / HA / SiRNA; 5) mixing the DNPs / Clolar / AS1411 / HA / SiRNA with DOX to obtain DNPs / Clolar / AS1411 / HA / SiRNA / DOX.

[0035] In the present invention, tryptophan-phenylalanine dipeptide DNPs are self-assembled to form self-assembled DNPs.

[0036] In the present invention, the tryptophan-phenylalanine dipeptide DNPs is preferably made by combining tryptophan-phenylalanine dipeptide and ZnCl 2 The zinc ions in are obtained through coordinat...

Embodiment 1

[0046] The dipeptide Try-Phe was purchased from Beijing Saibaisheng Gene Technology Co., Ltd. with a purity of 99.51%. DNA sequences (shown in Table 1) were synthesized by Sangon Biotechnology Co., Ltd (Shanghai, China). RNA sequences (shown in Table 1) were purchased from TaKaRa Biotechnology Co., Ltd. (Dalian, China). Clofarabine (Clolar) was purchased from Wuhu Huaren Technology Co., Ltd. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) were purchased from Aladdin. Influenza hemagglutinin peptide (HA, GLFGAIAGFIENGWEGMIDGWYG) was provided by GenScript Biotechnology Co., Ltd. (Nanjing). All other reagents were of analytical grade and used directly without further purification, and all water used in the experiments was sterile ultrapure water.

[0047] Preparation of DNP

[0048] Tryptophan-phenylalanine (Trp-Phe) dipeptide lyophilized powder was dissolved in isopropanol at a concentration of 5 mg / mL as a fresh stock soluti...

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Abstract

The invention provides a peptide nanoparticle capable of lysosome escape and its preparation method and application, belonging to the technical field of targeted drugs. Surface attachment of alanine dipeptide nanoparticles with AS1411 aptamer, influenza hemagglutinin peptide HA and antitumor drugs. The peptide nanoparticle of the present invention can effectively target and treat tumors, and has good low toxicity and biocompatibility; it can improve the accumulation of drugs in tumor sites on the basis of tumor visualization, and finally through the synergy of multiple drugs function to inhibit tumor growth. The peptide nanoparticles provided by the present invention can be used for both therapy and bioimaging.

Description

technical field [0001] The invention belongs to the technical field of targeted drugs, and in particular relates to a peptide nanoparticle capable of lysosome escape and its preparation method and application. Background technique [0002] Targeted drug carriers usually enter cells to form endosomes through endocytosis, and then develop into lysosomes through various mechanisms. Since general targeted drugs do not have membrane-soluble peptides, the main obstacle is the limitation of endoplasmic lysosomal packaging. Lysosomes contain a large number of degradative enzymes, which will lead to many nanomedicines, especially those with good biocompatibility, for example, nucleic acids tend to be enzymatically degraded, resulting in reduced or no cytosol release. Therefore, a robust strategy to improve nucleic acid delivery to escape and release from endolysosomes for efficient nucleic acid delivery is urgently needed. Contents of the invention [0003] In view of this, the o...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/54A61K47/64A61K47/69A61K31/704A61K31/7076A61K31/7088A61P35/00A61K49/00
CPCA61K47/549A61K47/6415A61K47/64A61K47/6929A61K31/704A61K31/7076A61K31/7088A61P35/00A61K49/0093A61K49/0056A61K2300/00
Inventor 郭英姝胡银华张书圣
Owner LINYI UNIVERSITY
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