This article summarizes recent progress in the design and synthesis of various oxidation-responsive polymers and their application in biomedical fields.

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 H 2 O 2 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 H 2 O 2 concentration. Nanoparticles which are extremely sensitive to the biorelevant concentration of H 2 O 2 (50 μM) at pH 7.4 were obtained, suggesting great promise for inflammationspecific drug delivery.

We report the synthesis of a new type of amphiphilic poly(amino ester)s which can be completely degraded in aqueous media via H 2 O 2 oxidation. The polymers were prepared by the controlled Michael-type addition polymerization of a phenylboronic pinacol ester-containing diacrylate and N-aminoethylpiperazine, followed by postmodification with mPEG5K-succinimide ester. Upon oxidation, the side chain phenylboronic esters will be transformed into phenol groups which can trigger the sequential selfimmolative process to degrade the polymer main chain. Meanwhile, the amino groups on the polymer main chain are capable of trapping the highly active quinone methides generated in situ during the oxidative degradation of the polymers. Based on the detailed oxidation kinetics and products of several model compounds, the H 2 O 2 -triggered degradation of nanoparticles of these copolymers was investigated by NMR spectroscopy, GPC, and Nile red fluorescence probe. The results demonstrate that the poly(amino ester) backbones were completely degraded by H 2 O 2 , resulting in the dissociation of nanoparticles. Oxidative degradation rates of the nanoparticles could be accelerated by increasing the concentration of H 2 O 2 , the PEGylation degree, or the pH of the buffer. Interestingly, the in situ formed quinone methides could be captured by secondary amines due to their higher nucleophilicity than H 2 O. Of potential importance, these amphiphilic oxidation-responsive copolymers are sensitive to stimulation of 200 μM H 2 O 2 ; therefore, they may find application in the field of intelligent drug/gene delivery systems.