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 multicomponent 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 phenylboronic acid ester was integrated into the polymer backbone by the in situ formed benzyl ester bond. GPC and 1H 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 P1, 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.