PLGA-based dual targeted nanoparticles enhance miRNA transfection efficiency in hepatic carcinoma

• DOI: 10.1038/srep46250
• Publication Date: 2017-04-07T11:16:13Z
• Authors: Chenlei Cai; Yuexia Xie; liangliang Wu; Xiaojing Chen; Hongmei Liu; Yan Zhou; Hanbing Zou; Dejun Liu; Yanan Zhao; Xianming Kong; Peifeng Liu
• Keywords: PLGA

Abstract Hepatic carcinoma (HCC) is a lethal disease associated with high morbidity and poor prognosis. Recently years, gene therapies have offered novel modalities to improve the prognosis of HCC patients. MicroRNA-99a (miR-99a) frequently down-regulated in HCC, where it acts as tumor suppressor. Therefore, we constructed monomethoxy (polyethylene glycol)-poly(D,L-lactide- co -glycolide)-poly(L-lysine)-lactobionic acid- anti-vascular endothelial growth factor antibody (mPEG-PLGA-PLL-LA/VEGFab or PEAL-LA/VEGFab) nanoparticles (NPs) highly specific targeting properties carriers restore expression miR-99a both vitro vivo , inhibit progression. In PEAL-LA/VEGFab NPs showed more efficient delivery HepG2 cells than conventional transfection reagent Lipofectamine TM 2000 (Lip2000). The higher efficiency consequently resulted down-regulation target genes suppression proliferation, migration invasion cells. miR-99a-PEAL-LA/VEGFab inhibited xenograft HCC-bearing mice without causing obvious systemic toxicity. Our results demonstrate that selectively effectively deliver based on double-targeting character these nanoparticles, thereby offering potential for translation into effective clinical HCC.