Cu-doped cerium oxide-based nanomedicine for tumor microenvironment-stimulative chemo-chemodynamic therapy with minimal side effects

CeO2 nanoenzyme possesses multiple enzyme-mimicking activities and excellent biocompatibility. However, its weak peroxidase (POD)-mimicking property in the tumor microenvironment (TME) hinders its further tumor therapy application. To enhance CeO2 nanoenzyme's POD activity and overcome limitations of single therapeutic modality, a novel antitumor controlled drug release system (CCCs NPs) was designed using Cu doped cerium oxide nanoparticles (Cu-CeO2 NPs) loaded with clinical anti-cancer drug doxorubicin (DOX) as the core and the breast cancer cell membrane as the outer shell. Cu doping endowed CeO2 NPs' with significantly enhanced PODmimicking activity in the TME due to a remarkably higher Ce3+/Ce4+ ratio. The cancer cell membrane coating enabled our nanomedicine with homotypic targeting property. Combined with chemotherapeutic drug DOX, a selective and nearly complete tumor suppression was demonstrated in vitro and in vivo. Remarkably, under physiological condition, CCCs NPs worked as a radical scavenger to protect normal cells from oxidative stress caused by anti-cancer drug DOX and center dot OH generated via Fenton-like reaction. Collectively, our CCCs NPs offered a therapeutic potential for effective breast cancer therapy while being free of side effects.

Automated summary

Cu-doped cerium oxide nanoparticles loaded with doxorubicin and coated with breast cancer cell membrane were designed as a novel antitumor controlled drug release system, showing enhanced peroxidase-mimicking activity in the tumor microenvironment. This system demonstrated selective and nearly complete tumor suppression both in vitro and in vivo, while also protecting normal cells from oxidative stress.