Activatable photosensitizers that can be activated by cancer-associated stimuli have drawn increasing attention for simultaneous fluorescence imaging and photodynamic ablation of cancer cells. Here, we developed a cancer-cell specific photosensitizer nano-delivery system by synthesizing protoporphyrin IX (PplX)-conjugated pullulan (P) with reducible disulfide bonds. The amphiphilic P-s-s-PpIX conjugate self-assembled in aqueous condition to form core-shell structured nanoparticles (P-s-s-PpIX NPs) with average size of 166 nm, showing reduction-controllable stability. In in vitro, the photoactivity of P-s-sPpIX NPs in an aqueous environment was significantly suppressed by the self-quenching effect, which kept P-s-s-PpIX NPs in a photo-inactive and quenched state. But in the presence of GSH, P-s-s-P-pIX NPs quickly dissociated by reductive breakage of disulfide linkers, followed by the significant recovery of fluorescent emission and singlet oxygen generation. In MCF-7 cells, compared to non-reducible P-PpIX NPs with stable amide linkages, P-s-s-PpIX NPs displayed higher cytotoxicity and induced higher apoptosis rate of tumor cells with light irradiation treatment. As a result, the P-s-s-PpIX NPs may serve as an effective smart nanomedicine platform for specific light-up and reduction-triggered cancer imaging and photodynamic therapy with the prominently reduced damage to normal tissues and cells. (C) 2017 Elsevier Inc. All rights reserved.