Non‐Fenton‐Type Hydroxyl Radical Generation and Photothermal Effect by Mitochondria‐Targeted WSSe/MnO₂ Nanocomposite Loaded with Isoniazid for Synergistic Anticancer Treatment

Abstract

Abstract Here, in terms of the highly reactive oxidative hydroxyl radical (•OH) generation ability of isoniazid (INH) catalyzed by Mn 2+ ion and the photothermal effect of WSSe nanoflakes, a WSSe/MnO 2 ‐INH nanocomposite for synergistic anticancer treatment is developed. Advanced INH‐induced •OH formation ability is systemically demonstrated in the presence of manganese and relevant non‐Fenton‐type mechanism, and good photothermal conversion efficiency of the WSSe/MnO 2 nanocomposite. After modifying with mitochondria‐targeted triphenylphosphonium bromide (TPP) moieties and camouflaging with cancer cells membrane (WSSe/MnO 2 ‐INH‐TPP@CM), it confers a sequential cell‐to‐mitochondria targeting ability. In vivo X‐ray computed tomography and magnetic resonance tumor imaging capability of the nanocomposite are also revealed. The mitochondria‐targeted oxidative damage and photothermal therapy by WSSe/MnO 2 ‐INH‐TPP@CM results in excellent anticancer treatment efficacy both in vitro and in vivo. This is the first exploration of the possibility of non‐Fenton‐type •OH formation for anticancer treatment, which opens new opportunities for ROS‐based and combined cancer treatment strategies.