Oxidation-Accelerated Hydrolysis of the Ortho Ester-Containing Acid-Labile Polymers

We report a versatile method to tune the hydrolysis of the ortho ester-containing block copolymers by covalently incorporating oxidation-sensitive phenylboronic ester units. A series of block copolymers which contain a polyethylene glycol (PEG) block and a hydrophobic segment composed of different amounts of pendent ortho ester and phenylboronic ester groups were synthesized. These copolymers can self-assemble into narrowly dispersed micelle-like nanoparticles in phosphate buffer. The kinetics of phenylboronic ester oxidation and ortho ester hydrolysis in the nanoparticles were studied at different pH and H2O2 concentration. The results indicated that the phenylboronic ester oxidation rate was faster than the ortho ester hydrolysis rate at neutral pH, and both processes were accelerated with increasing H2O2 concentration. Nanoparticles which are extremely sensitive to the biorelevant concentration of H2O2 (50 μM) at pH 7.4 were obtained, suggesting great promise for inflammation-specific drug delivery.