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

Colloids Surf B Biointerfaces. 2021 Sep:205:111878. doi: 10.1016/j.colsurfb.2021.111878. Epub 2021 May 24.

Abstract

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 POD-mimicking 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 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.

Keywords: Cancer cell membrane; Cerium oxide; Chemo-chemodynamic therapy; Metal doping; Nanoenzyme.

MeSH terms

  • Cell Line, Tumor
  • Cerium*
  • Doxorubicin / pharmacology
  • Humans
  • Nanomedicine
  • Nanoparticles*
  • Tumor Microenvironment

Substances

  • Cerium
  • ceric oxide
  • Doxorubicin