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@NP_Ce6/DOX was explored to realize remotely controlled drug release by light-activated size shrinkage. The TK-PPE@NP_Ce6/DOX encapsulating chlorin e6 (Ce6) and doxorubicin (DOX) was self-assembled from an innovative ROS-sensitive polymer TK-PPE with the assistance of an amphiphilic copolymer poly­(ethylene glycol)-b-poly­(ε-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@NP_Ce6/DOX core. Consequently, the size of TK-PPE@NP_Ce6/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.