Pure drug-assembled nanomedicines (PDANs) are currently under intensive investigation as promising nanoplatforms for cancer therapy. However, poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation. Herein, we report a core-matched nanoassembly of pyropheophorbide a (PPa) for photodynamic therapy (PDT). Pure PPa molecules are found to self-assemble into nanoparticles (NPs), and an amphiphilic PEG polymer (PPa-PEG) is utilized to achieve core-matched PEGylating modification the stacking effect and hydrophobic interaction between the PPa core and the PPa-PEG shell. Compared to PCL-PEG with similar molecular weight, PPa-PEG significantly increases the stability, prolongs the systemic circulation and improves the tumor-homing ability and ROS generation efficiency of PPa-nanoassembly. As a result, PPa/PPa-PEG NPs exert potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model. Together, such a core-matched nanoassembly of pure photosensitizer provides a new strategy for the development of imaging-guided theragnostic nanomedicines.