Trackable Water-Soluble Prodrug Micelles Capable of Rapid Mitochondrial-Targeting and Alkaline pH-Responsive Drug Release for Highly Improved Anticancer Efficacy

A trackable water-soluble prodrug conjugate possessing high contents of chlorambucil (Cb) and triphenylphosphonium cation (TPP) was designed and developed after TPP modification on the "branch" of amphipathic prodrugs based on convenient synthesis of heterobifunctional clickable poly(ethylene glycol) (PEG). The aqueous self-assembly of fluorescent polymeric micelles along precise composition can be easily prepared after directly dissolved (DD) in aqueous solution, and exhibit superior cytotoxicity to cancer cells along with highly improved selectivity and sensitivity because of their rapid mitochondrial-targeting and alkaline pH-responsive drug release capabilities. Notably, efficient codelivery of doxorubicin (DOX) for synergistic targeted drug delivery and cancer therapy was achieved.