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

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.