Phenylboronic acid-containing block copolymers: synthesis, self-assembly, and application for intracellular delivery of proteins

Abstract

The boronic acid group has been known to bind to sugars and living animal cells. Herein, a novel amphiphilic block copolymer poly(2-lactobionamidoethyl methacrylate)-block-poly(3-acrylamidophenylboronic acid) (p(LAMA-b-AAPBA)) was prepared by reversible addition fragmentation chain transfer (RAFT) polymerization. Due to the interaction between lactose moieties and phenylboronic acid moieties in p(LAMA-b-AAPBA), the copolymer could easily form nanoparticles in a spherical shape. The p(LAMA-b-AAPBA) nanoparticles had mean sizes from 238 to 403 nm with a zeta potential of about −20 mV. To study the feasibility of p(LAMA-b-AAPBA) nanoparticles acting as the potential nanocarrier for protein delivery, insulin, as a drug model, was encapsulated into the nanoparticles, the loading capacity was about 11%. Moreover, the nanoparticles demonstrated a sustained release of insulin and had no cytotoxicity on Chinese hamster ovary cells (CHO) and human colorectal carcinoma (Caco-2) cells. Confocal laser scanning microscopy showed that the nanoparticles could be taken up by Caco-2 cells, indicating that the stimuli-response of phenylboronic acid to carbohydrates on the cell surface facilitated the nanoparticles to bind to Caco-2 cells. Thus, the p(LAMA-b-AAPBA) nanoparticles can be considered as a promising carrier for protein transport.