Cell membrane camouflaged cerium oxide nanocubes for targeting enhanced tumor-selective therapy

Anticancer therapies with profound efficacy but negligible toxicity are a fundamental pursuit that has been made humanly possible through either targeting or tumor-selective therapeutic (TST) approaches. Herein, we developed a targeting-enhanced tumor-selective cancer therapy aimed at integrating the two approaches by preparing cerium oxide (CeO₂) nanocubes with glucose oxidase (GOx) modified on the cube surface and cancer cell membrane (CCM) camouflaged outside. The immune escape and homotypic binding of camouflaged CCM enable targeted delivery of the resultant CeO₂-GOx@CCM nanoparticles mostly into cancer tissue, while its acidic environment (pH < 6.6) activated a cascade reaction, in which the glucose was first catalyzed by GOx into H₂O₂ and then by CeO₂ into highly cytotoxic ˙OH killing cancer cells. In the case of off-targeting, when very few CeO₂-GOx@CCM nanoparticles were accidentally delivered into normal tissue, its neutral pH environment (pH = 7.4) triggered a protective reaction, in which the H₂O₂ generated was catalyzed by CeO₂ into non-toxic H₂O and O₂. Both in vitro and in vivo results demonstrated that this targeting-enhanced TST achieved the most remarkable antitumor performance with negligible toxic side effects.