Self-immolative PEGylated dendritic drug conjugates for cancer therapy with enhanced cellular uptake

A hypoxia-responsive nanomedicine NM-CB/Ce6 with prominent biocompatibility for co-delivering chlorambucil (CB) and chlorin e6 (Ce6) was prepared using a self-immolative PEGylated dendritic drug conjugate block-dendritic-polymer. Upon 650 nm near-infrared light (NIR) irradiation, the encapsulated Ce6 consumes oxygen to generate singlet oxygen (¹O₂) for photodynamic therapy (PDT). Under NIR-induced aggravated hypoxia, this nanomedicine can facilitate cellular internalization owing to hypoxia-responsive dePEGylation, and further disintegrate inside HepG2 cells to rapidly release activated CB for chemotherapy (CT).