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Photo-Reactive Oxygen Species Boosting Strategy By Employing Mitochondrial Targeting Zinc-Doped Magnetic Nanoparticles To Enhance Anti-Cancer Therapy

Congyu Wu, Ying Li, Jingjing Wang, Mengwei Chen, Yajing Shen, Yu Han, Maciej S. Lesniak, Yu Cheng

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The peroxidase-like functionality of iron oxide (IO) nanoparticles has attracted substantial attention in cancer treatment by reactive oxygen species (ROS) catalytic over-generation. However, the inefficient intracellular ROS generation still hurdles ready-to-use application of IO nanoparticles, attributing to the transient lifetime and limited diffusion distance of ROS. Indeed, excessive ROS generation in mitochondria is desirable to enhance cell death against cancer cells. In this study, we designed zinc-doped magnetic nanoparticles (MNPs) conjugated with triphenylphosphonium (TPP) for mitochondrial targeting. Moreover, the nanoparticles with high absorbance in visible region can catalyze ROS overproduction under visible light irradiation. Our platform provides a novel application of MNPs in targeted cancer therapy, which serves as a light-controlled switch to accelerate ROS generation and induce incremental cellular death.