An Oxygen Self‐Evolving, Multistage Delivery System for Deeply Located Hypoxic Tumor Treatment

The hypoxia-induced resistance to radiotherapy (RT) is a great threat to cancer patients. Therefore, overcoming the hypoxia tumor microenvironment is a vital issue. Herein, spindle-shaped CuS@CeO2 core-shell nanoparticles combining self-supplied oxygen, photothermal ability, and RT sensitive to cancer therapy are introduced. The spindle shape of CuS@CeO2 core-shell nanoparticles can potentiate their tumor penetration and subsequent internalization by cancer cells. The presence of CeO2 , functioning as a nanoenzyme, catalyzes the endogenous H2 O2 in tumor tissue into O2 , which remodels the hypoxic microenvironment into one susceptible to RT. CuS nanoparticles encapsulated in CeO2 undergo a steady release and deep tumor penetration, allowing the regression of lesions less affected by RT. Furthermore, in vitro and in vivo studies reveal that the design not only mitigates the dosage of RT, but more importantly allows the entire tumor to be treated without relapses.