Galactose-modified enzymatic synthesis of poly(amino-co-ester) micelles for co-delivery miR122 and sorafenib to inhibit hepatocellular carcinoma development

Abstract Nanomaterials as drug carriers hold promise for the treatment of carcinomas, but integrating multiple functions into a single vector is difficult. In this study, we aim to develop efficient materials as vectors for co-delivery of microRNA-122 (miR-122) and sorafenib (SRF). We successfully synthesized amphiphilic galactose-modified PEGylated poly(amino-co-ester) (Gal-PEG-PPMS) copolymers consisted of hydrophilic Gal-PEG5k chain segments and hydrophobic poly(ω-pentadecalactone-co-N-methyldiethyleneamine-co-sebacic acid) chain segments, which self-assembled to form cationic micelles at pH 5.2. The results showed that the micelles could encapsulate SRF and bind miR122 simultaneously, increase cellular uptake efficiency. Furthermore, the micelles showed favorable transfection efficiency in enhancing miR122 expression level, the migration and invasion ability of hepatocellular carcinoma (HCC) cells were significantly inhibited after being transfected with miR122-loaded micelles. Most importantly, the co-delivery micelles decreased cell activities of HepG2 cells, which was more effective than miR122 or SRF loaded micelles alone. Collectively, Gal-PEG-PPMS nanoparticles are promising multifunctional carriers for miR122 and SRF co-delivery system to treat HCC.