ROS-Sensitive Polymeric Nanocarriers with Red Light-Activated Size Shrinkage for Remotely Controlled Drug Release

Drug delivery systems with remotely controlled drug release capability are rather attractive options for cancer therapy. Herein, a reactive oxygen species (ROS)-sensitive polymeric nanocarrier TK-PPE@NPCe6/DOX was explored to realize remotely controlled drug release by light-activated size shrinkage. The TK-PPE@NPCe6/DOX encapsulating chlorin e6 (Ce6) and doxorubicin (DOX) was self-assembled from an innovative ROS-sensitive polyiner TK-PPE with the assistance of an amphiphilic copolymer poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG-b-PCL). Under the 660 nm red light irradiation, ROS generated by the encapsulated Ce6 were capable,of cleaving the TK linker in situ, which resulted in the rapid degradation of the TK-PPE@NPCe6/DOX core. Consequently, the size of TK-PPE@NPCe6/DOX shrank from 154 +/- 4 nm to 72 +/- 3 nm, and such size shrinkage affected further triggered rapid DOX release. As evidenced by both in vitro and in vivo experiments, such ROS-sensitive polymeric nanocarriers with light-induced size shrinkage capability offer remarkable therapeutic effects in cancer treatment. This concept provides new avenues for the development of light-activated drug delivery systems for remotely controlled drug release in vivo.