TME-responded Full-biodegradable nanocatalyst for mitochondrial calcium Overload-induced hydroxyl radical bursting cancer treatment

Mitochondrial calcium ions (Ca 2+ ) overload, an abnormal accumulation of free Ca 2+ in mitochondrial, has become a potential strategy for effective cancer treatment. Inspired by mitochondrial Ca 2+ overload-induced ROS generation, a tumor microenvironment (TME)-responded full-degradable [email protected] 2 O-TPP NCs are successfully fabricated for effective chemodynamic therapy (CDT) via toxic hydroxyl radical ( ∙ O H ) bursting. The as-synthesized nanocatalysts are stable and safe in normal tissues but will quickly degrade into Ca 2+ and cuprous ions (Cu + ) under the acidic TME. The mitochondrial Ca 2+ overload effectively simulates extra H 2 O 2 generation. Then Cu + catalyzes the produced H 2 O 2 into toxic ∙ O H to kill the tumor cells via Fenton-like reaction. Meanwhile, abundant GSH in tumor cells can further reduce Cu 2+ into Cu + to enhance the CDT effect. Both in vitro and in vivo evaluations demonstrate the efficient anti-tumor effect of [email protected] 2 O-TPP NCs via mitochondrial Ca 2+ overload-induced ∙ O H bursting. We believe that the development of [email protected] 2 O-TPP NCs will be an amazing inspiration for designing safe and green chemodynamic nanocatalysts for highly efficient cancer treatment.