A Harmless–Harmful Switchable and Uninterrupted Laccase‐Instructed Killer for Activatable Chemodynamic Therapy
Tian‐Jiao Zhou, Yue Xu, Lei Xing, Yi Wang, Hu‐Lin Jiang
Abstract
Abstract Chemodynamic therapy (CDT) employs Fenton catalysts to kill cancer cells by converting intracellular hydrogen peroxide (H 2 O 2 ) into hydroxyl radicals (OH•). Although many studies on H 2 O 2 supplementation have been conducted to improve the therapeutic effect of CDT, few studies have focused on the application of superoxide radical (O 2 −• ) in CDT, which may result in better efficacy. A major concern about O 2 −• ‐mediated CDT is its tendency to induce serious oxidative damage to normal tissues, which may be addressed by using a degradable O 2 −• scavenger. Here, a harmless‐harmful switchable and uninterrupted laccase (LAC)‐instructed killer (HULK) is constructed, which is the first CDT agent accelerated by LAC‐instructed O 2 −• generation and possesses a harmless‐harmful switchable effect because of the photodegradation of the O 2 −• scavenger iron‐chlorin e6 (FeCe6). LAC‐instructed substrate oxidation effectively catalyzes O 2 −• production with the help of intracellular reduction, thereby promoting the conversion of Fe 3+ to Fe 2+ , accelerating the generation of OH•, and inducing tumor cell apoptosis and necrosis. The introduced O 2 −• scavenger FeCe6 is quickly photodegraded during irradiation, while LAC‐instructed O 2 −• generation proceeds as before, resulting in activatable CDT. This work not only provides the first strategy for LAC‐instructed O 2 −• generation but also presents new insight into activatable CDT.