Drug delivery and application of tumor-inhibiting miRNAs by targeting tumor-associated macrophages

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...

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

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