Targeted siRNA delivery bionic nanoparticle as well as preparation method and application thereof

A technology of biomimetic nanoparticles and composite nanoparticles, which is applied in the field of targeted delivery of siRNA biomimetic nanoparticles, to achieve the effect of inhibiting proliferation and efficient silencing

Pending Publication Date: 2019-12-13
GUANGZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In addition, studies have shown that the degradation half-life of PBAE under physiological conditions is only half an hour

Method used

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  • Targeted siRNA delivery bionic nanoparticle as well as preparation method and application thereof
  • Targeted siRNA delivery bionic nanoparticle as well as preparation method and application thereof
  • Targeted siRNA delivery bionic nanoparticle as well as preparation method and application thereof

Examples

Experimental program
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Embodiment 1

[0057] Example 1: Preparation of homotype targeting biomimetic nanoparticles

[0058] (1) Synthesis of PBAE. 1,4-Butanediol diacrylate was mixed with 4-amino-1-butanol, and polymerized by Michael addition reaction at 90° C. for 24 hours. The monomer acrylate-amine ratio is 1.1:1. The resulting product was dissolved in anhydrous tetrahydrofuran at a concentration of 100 mg / mL. An excess of small molecule 1-(3-aminopropyl)-4-methylpiperazine with an amine concentration of 0.2M was added to the solution as a polymer capping group, and the reaction was stirred at room temperature for 1 hour. After the reaction, the inventors added ether to the product to wash away excess monomer. The PBAE was collected, washed repeatedly with ether, and dried in vacuo.

[0059] (2) Extraction of NCI-H1299 cell membrane. NCI-H1299 cell membranes were obtained by repeated freezing and thawing. First, NCI-H1299 cells were collected and washed 3 times with PBS solution containing protease inhi...

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Abstract

The invention provides a targeted siRNA delivery bionic nanoparticle which is a PBAE / siRNA composite nanoparticle wrapped by a cancer cell membrane, and further provides a preparation method and application thereof. According to the method, bionic nanoparticles are adopted, silencing of the Plk1 gene is efficiently achieved, apoptosis of cancer cells is induced, and proliferation of the cancer cells is inhibited. According to the method disclosed by the invention, a system capable of realizing efficient siRNA delivery is constructed. The polypeptide can specifically recognize homotype cancer cells, accumulate in the cancer cells, successfully escape from lysosome after entering the cells, efficiently silence target genes and inhibit expression of the target genes to cause cancer cell apoptosis, thereby inhibiting tumor growth.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a targeted delivery siRNA biomimetic nanoparticle, a preparation method and application thereof. Background technique [0002] Based on new discoveries about tumor pathogenesis, gene therapy has been considered as a potential cancer treatment. However, successful gene therapy, such as the widely used RNA interference (RNAi), relies heavily on efficient transfection. Without a doubt, viral vectors are considered the most effective tools in this field. However, the inherent toxicity, immunogenicity and tumorigenicity of viruses have raised concerns about their safety. Based on the excellent properties of non-viral vectors such as convenient design, smart reactivity and low cytotoxicity, they have great prospects in gene delivery. Good substitute. Many existing vectors show high transfection ability in vitro, but their performance is severely weakened when they encounter comp...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K9/51A61K47/46A61K31/7088A61P35/00B82Y5/00B82Y20/00B82Y30/00B82Y40/00
CPCA61K47/6935A61K9/5068A61K31/7088B82Y5/00B82Y30/00B82Y20/00B82Y40/00A61P35/00
Inventor 张灵敏余细勇邓赛林忠晓
Owner GUANGZHOU MEDICAL UNIV
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