Lipid Nanoparticles Composed of Quaternary Amine-Tertiary Amine Cationic Lipid Combination (QTsome) for Therapeutic Delivery of AntimiR-21 for Lung Cancer.

Yung BC, Li J, Zhang M, Cheng X, Li H, Yung EM, Kang C, Cosby LE, Liu Y, Teng L, Lee RJ
Mol Pharm 13 653-62 02/01/2016

Abstract

MicroRNA-21 (miR-21) is an oncomiR that is frequently upregulated in human cancers. AntimiR-21 (AM-21) is an oligonucleotide complementary to miR-21 that is designed to inhibit its gene silencing activities. To facilitate efficient delivery of AM-21, a novel lipid nanoparticle formulation called QTsome, based on a combination of quaternary amine and tertiary amine cationic lipids, with a distinctive pH-responsive profile, was developed. QTsome/AM-21 comprising DODMA/DOTAP/DOPC/CHOL/mPEG-DPPE and AM-21 oligonucleotide exhibited a mean particle diameter of below 150 nm, moderate zeta potential (+13.2 mV), excellent colloidal stability, and high drug loading efficiency (above 80%). In vitro study showed QTsome/AM-21 induced upregulation of miR-21 targets, including PTEN and DDAH1, in A549 cells while increasing their sensitivity toward paclitaxel (PTX). Finally, tumor regression, prolonged survival, and miR-21 target upregulation were demonstrated in an A549 xenograft mouse model. These data suggest that QTsome/AM-21 warrants further evaluation as an anticancer agent.

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