Herein, a novel nano-system IF7-ROSPCNP, which is O₂-evolving and reactive oxygen species (ROS)-activable, was developed for enhancing the combination chemotherapy and photodynamic therapy (PDT). The nanoparticles composed of photosensitizers (disulfonated meso-tetraphenylporphine, TPPS2a) and catalase in the inner core, doxorubicin (DOX) in the polymeric shell and functionalized on its surface with IF7 peptide, which specially bind to annexin 1. As confirmed that the structure of IF7-ROSPCNP was able to remain intact under normal physiological conditions. After IF7-ROSPCNP was selectively entrapped by the annexin 1-positive and ROS-abundant MCF-7/ADR cells, the shell of nanoparticles was ruptured and the entrapped photosensitizers were completely released out. Under irradiation, ROS was continuously produced and the DOX, which was conjugated to the terminal of polylactic copolymer (mPEG-PLA) by a ROS-cleavable linkage, was subsequently released. With such strategy, cellular uptake of drugs was dramatically improved resulted in an enhanced cytotoxicity and anti-tumor effect on drug resistant cancer.