Lipid Nanoparticles Composed of Quaternary Amine–Tertiary
Amine Cationic Lipid Combination (QTsome) for Therapeutic Delivery
of AntimiR-21 for Lung Cancer
posted on 2016-02-01, 00:00authored byBryant
C. Yung, Jilong Li, Mengzi Zhang, Xinwei Cheng, Hong Li, Elaine
M. Yung, Chen Kang, Lauren E. Cosby, Yang Liu, Lesheng Teng, Robert J. Lee
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.