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<sub>Ce6/DOX</sub> was explored to realize remotely controlled drug release by light-activated size shrinkage. The TK-PPE@NP<sub>Ce6/DOX</sub> 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)-<i>b</i>-poly­(ε-caprolactone) (PEG-<i>b</i>-PCL). Under the 660 nm red light irradiation, ROS generated by the encapsulated Ce6 were capable of cleaving the TK linker <i>in situ</i>, which resulted in the rapid degradation of the TK-PPE@NP<sub>Ce6/DOX</sub> core. Consequently, the size of TK-PPE@NP<sub>Ce6/DOX</sub> shrank from 154 ± 4 nm to 72 ± 3 nm, and such size shrinkage affected further triggered rapid DOX release. As evidenced by both <i>in vitro</i> and <i>in vivo</i> 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 <i>in vivo</i>.