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MicroRNA nanocomposites for treating colon cancer and preparation and application thereof

A nanocomposite, colon cancer technology, applied in gene therapy, medical preparations with inactive ingredients, medical preparations containing active ingredients, etc., can solve the problem of low surface charge density, no endosome escape function, nucleic acid drugs Weak load capacity and other problems, to achieve the effect of simple process, suitable particle size range and good biological safety

Inactive Publication Date: 2019-06-25
SHANGHAI LONGXIN BIOMEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, chitosan and its derivatives usually have low surface charge density, weak loading capacity for nucleic acid drugs, and no strong endosome escape function, so the delivery efficiency of nucleic acid drugs is low.

Method used

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  • MicroRNA nanocomposites for treating colon cancer and preparation and application thereof
  • MicroRNA nanocomposites for treating colon cancer and preparation and application thereof
  • MicroRNA nanocomposites for treating colon cancer and preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] The preparation of embodiment 1 n-octanoic acid-hydroxyethyl chitosan (C8-GC)

[0041] Dissolve 0.2g hydroxyethyl chitosan (Mw=5kDa) in 20mL DMSO to obtain a hydroxyethyl chitosan solution; dissolve 0.08g n-octanoic acid, 0.102g EDC, and 0.062g NHS in 10mL DMSO, and activate in an ice bath 0.5-1h, then slowly drop into the hydroxyethyl chitosan solution, adjust the pH to 8, react at room temperature for 24-48h, dialyze (MWCO=14kDa) for 48-72h, freeze-dry to obtain n-octanoic acid-hydroxyethyl chitosan Sugar (C8-GC).

Embodiment 2

[0042] The preparation of embodiment 2 n-octanoic acid-hydroxyethyl chitosan-guanidinoacetic acid (C8-GC-GA)

[0043] Dissolve 0.1 g of guanidinoacetic acid, 0.060 g of EDC, and 0.045 g of HOBT in 10 mL of PBS (pH 7.4), activate it in an ice bath for 0.5-1 h, and then slowly add it dropwise to 0.1 g of the intermediate product prepared in Example 1 In C8-GC, adjust the pH to 8, react at room temperature for 24-48 hours, dialyze (MWCO=14kDa) for 48-72 hours, and freeze-dry to obtain n-octanoic acid-hydroxyethyl chitosan-guanidinoacetic acid (C8-GC-GA).

Embodiment 3

[0044] The preparation of embodiment 3 polylactic acid-chitosan (PLA-G)

[0045] Dissolve 0.2g of chitosan (Mw=3kDa) in 20mL of 2% acetic acid to obtain a chitosan solution; dissolve 0.10g of polylactic acid, 0.136g of EDC, and 0.082g of NHS in 20mL of chloroform solution and activate under ice-bath conditions 0.5-1h, then slowly drop into the chitosan solution, adjust the pH to 8, react at room temperature for 24-48h, dialyze (MWCO=14kDa) for 48-72h, freeze-dry to obtain polylactic acid-chitosan (PLA-G) .

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Abstract

The invention relates to a method for preparing microRNA nanocomposites for treating colon cancer. The method comprises the steps of: dissolving a guanidinated amphiphilic chitosan derivative in an RNase-free aqueous phase solution to obtain a cationic micelle solution A; dissolving a target microRNA in the RNase-free aqueous phase solution to obtain a solution B; wherein the guanidinated amphiphilic chitosan derivative comprises a hydrophilic fragment, and the hydrophilic fragment is ligated with a hydrophobic fragment and a transmembrane functional group molecule, the hydrophilic fragment isa hydrophilic chitosan or chitosan derivative, and the transmembrane functional group molecule is a guanidyl-containing fatty acid; the target microRNA is a microRNA with low expression in colon cancer; evenly mixing the cationic micelle solution A with the solution B, and standing and incubating for 20-30 min at 35-40 oC. In the nanocomposites, a cationic micelle adsorbs microRNA by ionic electrostatic interaction to form a nanocomposite with passive targeting of microRNA for colon cancer, and the method has the advantages of simple and convenient preparation process, high microRNA entrapment efficiency and high targeting transfection efficiency and the like.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a microRNA nanocomplex for treating colon cancer and its preparation and application. Background technique [0002] Colorectal cancer is a common malignant tumor. Due to changes in dietary structure and lifestyle, the incidence of colorectal cancer in China, Japan and other Eastern countries has a tendency to increase. Most studies believe that the reason for the increase in the incidence of colorectal cancer is related to lifestyle changes such as high-fat diet and insufficient exercise. At present, chemotherapy drugs are mostly used in the treatment of colorectal cancer, but there is a lack of targeted therapy drugs for colorectal cancer, which makes the treatment effect poor and often causes irreversible damage to normal tissues. [0003] Tumor gene therapy is to introduce therapeutic nucleic acid into cells to modify gene information, which has gradually become an ...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K31/7105A61K47/36A61P35/00
Inventor 常英张彩华霍美蓉廉云飞殷婷婕褚旭新
Owner SHANGHAI LONGXIN BIOMEDICAL TECH CO LTD