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RNA nanoparticles and their application in the prevention and treatment of gastric cancer

A nanoparticle and particle technology, applied in the fields of application, nanotechnology, nanotechnology, etc., can solve the problems of difficult gastric cancer treatment application, biosafety of highly cytotoxic lentivirus, etc., and achieve inhibition of killing gastric cancer cells, efficient and specific delivery , enhance the effect of treatment

Active Publication Date: 2017-08-04
SHANGHAI JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The siRNA delivery carrier lipofectamin2000 and lentivirus involved in the above two technologies are limited by the high cytotoxicity of lipofectamin2000 and the potential biological safety of lentivirus in practical application, and it is still difficult to realize the application in the treatment of gastric cancer

Method used

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  • RNA nanoparticles and their application in the prevention and treatment of gastric cancer
  • RNA nanoparticles and their application in the prevention and treatment of gastric cancer
  • RNA nanoparticles and their application in the prevention and treatment of gastric cancer

Examples

Experimental program
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Effect test

Embodiment 1

[0036] Example 1 Realization of RNA Nanoparticles Carrying siRNA to Kill Gastric Cancer Cells

[0037] RNA nanoparticles carry siRNA into gastric cancer cells to kill gastric cancer cells and inhibit the growth of subcutaneous tumors in nude mice. The experimental method is as follows:

[0038] The first step, the construction of pRNA-3WJ RNA nanoparticles:

[0039] The RNA nanoparticles consist of three parts (see figure 1 ), the 5' ends of chain a, chain b and chain c were respectively covalently modified with folic acid molecule (as a targeting ligand), Alexa Fluor647 (near-infrared fluorescent indicator), and BRCAA1siRNA to make a3WJ , b3WJ and c3WJ three parts, the above three parts are produced by TriLink Company of the United States. The three parts a3WJ, b3WJ and c3WJ were mixed in DEPC-treated ultrapure water or TMS buffer (89mM Tris, 5mM MgCl2, pH7.6) at a molar ratio of 1:1:1. In order to purify dimers, trimers, and nanoparticles of 3WJ structure composed of the ...

Embodiment 2

[0057] Example 2 RNA nanoparticles as probes for imaging

[0058] In this embodiment, RNA nanoparticles labeled with a near-tracer (infrared dye) are used as living body fluorescence imaging probes (such as nude mice subcutaneously transplanted tumor models of gastric cancer), and the experimental method is as follows:

[0059] The first step, establishment of subcutaneous tumor model in nude mice

[0060] The method of the fifth step in Example 1 was used to establish the subcutaneous tumor model of the MGC-803 cell line in nude mice, and it was used for living fluorescent animal experiments when the volume of the tumor reached about 200 mm3.

[0061] RNA nanoparticles labeled with folic acid and near-infrared dye Alexa Fluor647 were intravenously injected into nude mice (according to the concentration of 32mg / kg body weight, adding about 200μl of 20nmol RNA nanoparticles dissolved in PBS buffer), 30 days after intravenous injection Minutes, 3 hours, 5 hours, 12 hours and 24...

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PUM

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Abstract

A RNA nanoparticle is disclosed. According to base pairing rules, a particle is formed from a chain RNA, b chain RNA and c chain RNA, wherein sequence of the a chain RNA is SEQ ID No.1; sequence of the b chain RNA is SEQ ID No.2; and sequence of the c chain RNA is SEQ ID No.3. It shows through experimental verification at the cellular and animal level that the RNA nanoparticle provided by the invention has good biosecurity and excellent gene interference effect and specificity, can effectively inhibit growth of gastric cancer cell lines and transplant subcutaneous sarcoma and can be applied in prevention, cure and diagnosis of stomach cancer.

Description

technical field [0001] The present invention relates to a biological nanoparticle, in particular to a RNA nanoparticle, a method for delivering siRNA in vivo and in vitro by using it as a carrier, and the in vivo fluorescence imaging of the RNA nanoparticle labeled with a near-infrared dye in a subcutaneous tumor model Applications Background technique [0002] Gastric cancer has the characteristics of high incidence, easy metastasis and high mortality. According to clinical statistics, the recurrence and metastasis rate of tumor after radical operation is as high as 33%. In China, the incidence of gastric cancer ranks second and the death rate ranks third. There are more than 1 million new cases of gastric cancer each year in the world, and about 800,000 deaths. China accounts for 42% of the world's new cases of gastric cancer each year, and 35% of deaths. Its morbidity and mortality are more than twice the world's average level. [0003] Gastric cancer originates from th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/00C07H21/02C07H1/00A61K31/713A61K49/00A61P35/00A61P1/00B82Y30/00B82Y40/00
Inventor 崔大祥张春雷郭培宣
Owner SHANGHAI JIAOTONG UNIV
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