Facile Synthesis of H2O2-Cleavable Poly(ester-amide)s by Passerini Multicomponent Polymerization

We report the straightforward synthesis of two types of H2O2-cleavable poly(ester-amide)s (P1 and P2) via the Passerini multi component polymerization (P-MCP) of 4-formylbenzeneboronic acid pinacol ester with 1,6-diisocyanohexane and 1,6-hexanedioic acid or a polyethylene glycol (PEG) dicarboxylic acid. The H2O2-cleavable phenyl boronic acid ester was integrated into the polymer backbone by the in situ formed benzyl ester bond. GPC and H-1 NMR confirmed the complete H2O2-triggered degradation of these polymers in aqueous medium by a mechanism of sequential oxidation of phenylboronic acid ester and self-immolative elimination. Compared with the hydrophobic polymer PI, the PEG-based water-soluble polymer P2 degraded much faster even at a lower H2O2 concentration. Cytocompatible nanoparticles of polymer P1 loaded with fluorescent Nile red were fabricated, and controlled release of Nile red in response to H2O2 was achieved, thus, demonstrating the utility of these polymers as potential H2O2 responsive delivery vehicles.