Hydrogen Peroxide-Activatable Nanoparticles for Luminescence Imaging and In Situ Triggerable Photodynamic Therapy of Cancer

Abnormally increased reactive oxygen species (ROS) are intimately related to the development and metastasis of cancer. Since hydrogen peroxide (H₂O₂) is a major component of ROS, molecular imaging and selective treatment in response to high H₂O₂ are intriguing for the management of cancers. Herein, we report novel self-assembly luminescent nanoparticles, which can be activated by H₂O₂, thereby serving as an effective nanotheranostics for luminescence imaging and in situ photodynamic therapy (PDT) of tumors with high H₂O₂. This functional nanomedicine was assembled from an amphiphilic conjugate (defined as CLP) based on chlorin e6 (Ce6) simultaneously conjugated with luminol and poly­(ethylene glycol), exhibiting a well-defined core–shell nanostructure. Upon triggering by pathologically relevant levels of H₂O₂, CLP nanoparticles produced luminescence due to the luminol unit and simultaneous excitation of Ce6 by chemiluminescence resonance energy transfer, enabling in vitro and in vivo imaging of tumors with highly expressed H₂O₂. In addition, excited Ce6 can produce singlet oxygen (¹O₂) for in situ PDT of H₂O₂-high tumors and inhibiting lung metastasis, which was demonstrated by in vitro and in vivo experiments. Furthermore, preliminary studies revealed the biosafety of CLP nanoparticles. Consequently, the self-illuminating nanoparticles are promising for noninvasive imaging and therapy of tumors with high expression of H₂O₂.