Reactive oxygen species-sensitive nanophotosensitizers of aminophenyl boronic acid pinacol ester conjugated chitosan-g-methoxy poly(ethylene glycol) copolymer for photodynamic treatment of cancer.

The aim of this study is to prepare reactive oxygen species (ROS)-sensitive nanophotosensitizers for targeted delivery of chlorin e6 (Ce6) and photodynamic therapy of tumor. For this purpose, thiodipropionic acid (TDPA) was conjugated with phenyl boronic acid pinacol ester (PBAP) (TDPA-PBAP conjugates) and then TDPA-PBAP conjugates were attached to the chitosan backbone of chitosan-g-methoxy poly(ethylene glycol) (ChitoPEG) copolymer (ChitoPEG-PBAP). Ce6-incorporated ChitoPEG-PBAP nanophotosensitizers have a ROS-sensitive manner in vitro. The size of ChitoPEG-PBAP nanoparticles increased or disintegrated in the responsive manner against H2O2 concentration. Ce6 release rate from ChitoPEG-PBAP nanophotosensitizers also increased by adding H2O2. These results indicated that nanophotosensitizers have sensitivity against ROS and showed triggered Ce6 release behavior. ChitoPEG-PBAP nanophotosensitizers can be more efficiently internalized into cancer cells compared to Ce6 alone and then produce ROS with a more efficient manner. Furthermore, ChitoPEG-PBAP nanophotosensitizers suppressed the viability of cancer cells in vitro and tumor growth in vivo with higher efficacy compared to Ce6 alone. Furthermore, ChitoPEG-PBAP nanophotosensitizers were efficiently delivered to irradiated tumor tissues, indicating that ChitoPEG-PBAP nanophotosensitizers can be delivered to the tumor with ROS-sensitive manner. We suggest that ChitoPEG-PBAP nanophotosensitizer is a promising candidate for PDT of cancers.