Photodynamic therapy(PDT)has been widely investigated for cancer therapy.The intracellular accumu-lation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis.However,there is growing evidence that the ubiquitin-proteasome pathway(UPP)significantly impedes PDT by prevent-ing the enrichment of ROS-damaged proteins in tumor cells.To tackle this challenge,we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib(BTZ,a pro-teasome inhibitor)and pyropheophorbide a(PPa)for proteasome inhibition-mediated PDT sensitization.The precisely engineered nanoassembly with the optimal dose ratio of BTZ and PPa demonstrates mul-tiple advantages,including simple fabrication,high drug co-loading efficiency,flexible dose adjustment,good colloidal stability,long systemic circulation,favorable tumor-specific accumulation,as well as sig-nificant enrichment of ROS-damaged proteins in tumor cells.As a result,the cooperative nanoassembly exhibits potent synergistic antitumor activity in vivo.This study provides a novel dual-drug engineering modality for multimodal cancer treatment.