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.