Activatable Singlet Oxygen Generation from Lipid Hydroperoxide Nanoparticles for Cancer Therapy

Abstract Reactive oxygen species (ROS)‐induced apoptosis is a widely practiced strategy for cancer therapy. Although photodynamic therapy (PDT) takes advantage of the spatial–temporal control of ROS generation, the meticulous participation of light, photosensitizer, and oxygen greatly hinders the broad application of PDT as a first‐line cancer treatment option. An activatable system has been developed that enables tumor‐specific singlet oxygen ( 1 O 2 ) generation for cancer therapy, based on a Fenton‐like reaction between linoleic acid hydroperoxide (LAHP) tethered on iron oxide nanoparticles (IO NPs) and the released iron(II) ions from IO NPs under acidic‐pH condition. The IO‐LAHP NPs are able to induce efficient apoptotic cancer cell death both in vitro and in vivo through tumor‐specific 1 O 2 generation and subsequent ROS mediated mechanism. This study demonstrates the effectiveness of modulating biochemical reactions as a ROS source to exert cancer death.