Cancer‐Thylakoid Hybrid Membrane Camouflaged Thulium Oxide Nanoparticles with Oxygen Self‐Supply Capability for Tumor‐Homing Phototherapy

Abstract Nanomaterials that generate reactive oxygen species (ROS) upon light irradiation have significant applications in various fields, including photodynamic therapy (PDT) that is widely recognized as a highly momentous strategy for the eradication of cancer cells. However, the ROS production rate of photosensitizers, as well as the tumor hypoxia environment, are two major challenges that restrict the widespread application of PDT. In this study, a cancer‐thylakoid hybrid membrane‐camouflaged thulium oxide nanoparticles (Tm 2 O 3 ) for tumor‐homing phototherapy through dual‐stage‐light‐guided ROS generation and oxygen self‐supply is developed. Tm 2 O 3 as a type II photosensitizer are viable for NIR‐stimulated ROS generation due to the unique energy levels, large absorption cross section, and long lifetime of the 3H4 state of Tm ions. The thylakoid membrane (TK) plays a catalase‐like role in converting hydrogen peroxide into oxygen and also acts as a natural photosensitizer that can generate lethal ROS through electron transfer when exposed to light. In addition, fluorescence dye DiR is embedded in the hybrid membrane for in vivo tracing as well as photothermal therapy. Results show that tumors in Tm 2 O 3 @TK‐M/DiR group are effectively ablated following dual‐stage‐light irradiation, highlighting the promising potential of rare‐earth element‐based type II photosensitizers in various applications.