In this work, novel amphiphilic diblock copolymers of polyethylene glycol and polyphosphoester with pendant thioether groups, denoted as mPEG-b-PMSPEP, were synthesized through the ring-opening polymerization of functionalized cyclic phosphoester monomer using methoxy poly(ethylene glycol) and Sn(Oct)(2) as the macroinitiator and catalyst, respectively. The successful synthesis was confirmed by H-1,C-13, P-31 nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). These amphiphilic block copolymers self-assembled spontaneously in the aqueous solution, and the formed nanoparticles were sensitive to the oxidation that induced the hydrophobic to hydrophilic transition for its PMSPEP core under triggering of H2O2 and the subsequent dissociation of the nanoparticles. In addition, the reactive oxygen species (ROS) generated by light and the photosensitizer were also capable of carrying out the oxidation of these nanoparticles. Their oxidation profiles were systemically evaluated by H-1 NMR Finally, the mPEG-b-PMSPEP nanoparticles were used to coencapsulate the photosensitizer chlorin e6 (Ce6) and anticancer drug paclitaxel (PTX), achieving the photoaccelerated PTX release via oxidation of the nanoparticles by the generated ROS under light irradiation. Meanwhile, the in vitro cytotoxicity assays indicated that these nanoparticles coencapsulated with PTX and Ce6 showed a combined cell-killing effect toward MDA-MB-231 tumor cells, exhibiting great potential for drug delivery systems that realize the synergistic chemo-photodynamic therapy for cancer treatment.