Chemoenzymatic Synthesis of Cholesterol-g-Poly(amine-co-ester) Amphiphilic Copolymer as a Carrier for miR-23b Delivery

The lipase-catalyzed polymerization of N-methyldiethanolamine, diethyl sebacate and w-pentadecanolide was performed to construct a cationic poly(amine-co-ester), and a hydrophobic N-(2-bromoethyl)carbamoyl cholesterol was then grafted onto its main chain through a quaternization reaction to prepare the amphiphilic copolymer Chol-g-PMSC-PPDL. The copolymer efficiently bound and condensed miR-23b to form stable nanocomplexes, which showed favorable cellular uptake and miR-23b transfection efficacy due to the introduction of the hydrophobic segment. After miR-23b delivery, an obvious inhibition of cell proliferation could be induced, which was attributed to the induction of cell apoptosis and cell cycle arrest. Moreover, the carrier-mediated miR-23b delivery could inhibit the migration and invasion of tumor cells. Overall, the work provides a novel chemoenzymatic strategy for constructing biodegradable and biocompatible poly(amine-co-ester) derivatives, which are promising carriers for oligonucleotide delivery to achieve tumor gene therapy.