Drug delivering miRNA for suppressing tumor growth by targeting tumor-associated macrophages and application

A tumor-associated, macrophage-based technology applied in the field of oncology medicine

Inactive Publication Date: 2018-09-28
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, only a small number of miRNAs (for example, MIMAT0000135) with the function of selectively activating TAMs have been reported, but they have only been found to inhibit tumor growth against certain cancers, such as lung cancer, and they have been actually applied to clinical anti-tumor targets in vivo. Drugs are yet to be studied

Method used

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  • Drug delivering miRNA for suppressing tumor growth by targeting tumor-associated macrophages and application
  • Drug delivering miRNA for suppressing tumor growth by targeting tumor-associated macrophages and application
  • Drug delivering miRNA for suppressing tumor growth by targeting tumor-associated macrophages and application

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Embodiment Construction

[0037] The present invention will be described in further detail below in conjunction with the accompanying drawings and embodiments.

[0038] 1. Preparation of nanomedicines targeting tumor-associated macrophages to deliver miRNA

[0039] 1. Preparation of Cationized Glucomannan

[0040] 1) Accurately weigh 250 mg of glucomannan (KGM), and add it to a beaker filled with 12 mL of anhydrous dimethyl sulfoxide (DMSO);

[0041] 2) Put the beaker on the heating platform and heat it evenly until the glucomannan is completely dissolved, then stop the heating and wait for it to cool down to room temperature;

[0042] 3) Add 0.8 g of N'N-carbonyldiimidazole (N,N'-Carbonyldiimidazole, CDI) to the cooled DMSO solution containing glucomannan, and stir at room temperature for 1 h to activate the hydroxyl group of KGM ;

[0043] 4) Add 1.3mL of ethylenediamine to the activated KGM solution, and stir at room temperature for 12h;

[0044] 5) Select a dialysis bag with a molecular weight of...

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Abstract

The invention provides a drug delivering miRNA for suppressing tumor growth by targeting tumor-associated macrophages and application. The drug comprises a drug carrier targeting the tumor-associatedmacrophages, miRNA wrapped in the drug carrier and cationized polysaccharide with mannose residues. The sequences of the miRNA are as shown in SEQ. ID. NO. 1 or SEQ. ID. NO. 2. Through an in vitro experiment, miR-99b-5p which can promote M1 type activation of the macrophages and can inhibit M2 type activation of the macrophages is discovered, nano-material targeting tumor-associated macrophages (TAMs) is used for wrapping the miRNA, and the wrapped miRNA is directly transported to a mouse model of liver cancer through a tail vein, it is found that delivery of the miRNA to the targeted TAMs cansignificantly inhibit tumor growth, and delivery of the miR-99b-5p to the targeted TAMs has a better effect of inhibitory action on tumor growth than delivery of other miRNAs, such as miR-125a.

Description

technical field [0001] The invention relates to the field of tumor medicine, in particular to the function of targeting tumor-associated macrophages to deliver miRNA to inhibit tumor growth. Background technique [0002] Macrophages can be roughly divided into classically activated M1 macrophages and alternatively activated M2 macrophages. The former can be induced by LPS and IFN-γ, etc., and highly express marker molecules IL-12, TNF-α and IL -6, etc., play the role of clearing bacteria, antigen presentation, promoting inflammatory response and anti-tumor; the latter can be induced by IL-4, etc., and highly express marker molecules mannose receptor (MR), arginine Enzyme-1 and IL-10, etc., play the role of resisting parasitic infection, promoting tissue repair, inhibiting inflammatory response and promoting tumor. Intratumoral macrophages, also known as tumor-associated macrophages (TAMs), are an important part of the tumor inflammatory microenvironment. In most tumor tiss...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K31/7088A61K47/36A61P35/00
CPCA61K9/5161A61K31/7088A61P35/00
Inventor 秦鸿雁王亮赵俊龙韩骅
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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