title: Lipid Nanoparticles Composed of Quaternary Amine-Tertiary Amine Cationic Lipid Combination (QTsome) for Therapeutic Delivery of AntimiR-21 for Lung Cancer.
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.
authors.forename: Bryant C
authors.initials: BC
authors.lastname: Yung
authors.forename: Jilong
authors.initials: J
authors.lastname: Li
authors.forename: Mengzi
authors.initials: M
authors.lastname: Zhang
authors.forename: Xinwei
authors.initials: X
authors.lastname: Cheng
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Yung
authors.forename: Chen
authors.initials: C
authors.lastname: Kang
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Cosby
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Jilin University , Changchun, China.
authors.forename: Lesheng
authors.initials: L
authors.lastname: Teng
authors.affiliation: College of Life Sciences, Jilin University , Changchun, China.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
mesh_terms: D000588:Amines / Q000737:chemistry*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002412:Cations / Q000737:chemistry*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000588:Amines; D000972:Antineoplastic Agents, Phytogenic; D002412:Cations; D008055:Lipids; D008081:Liposomes; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D017239:Paclitaxel
keywords: RNA interference; cancer; drug delivery; gene regulation; microRNA; nanoparticles; noncoding RNA