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.