Cellular Microenvironment Triggered Ferroptosis and Photodynamic Therapy for Selective Senescent Cell Clearance

Biomedical strategies based on the cellular microenvironment often lead to significant improvements in diagnosis and therapy. In this study, based on the elevated reactive oxygen species (ROS) microenvironment of senescent cells, we designed Fe³⁺ coordinated nitrogen doped graphene quantum dots (Fe@N-GQDs) with both photodynamic and ferroptotic activity. The results demonstrated that Fe³⁺ modulated the electronic structure of nitrogen doped graphene quantum dots (N-GQDs) and enhanced their photodynamic activity. Meanwhile, the high ROS levels in endoplasmic reticulum and mitochondria enabled accumulated Fe@N-GQDs to synergistically amplify oxidative stress through the Fe³⁺/Fe²⁺ redox cycle and activate the ferroptosis related process. Under the synergistic photodynamic and ferroptosis effects, the clearance efficiency of senescent cells reached 98%. More importantly, leveraging the senescent cell microenvironment, Fe@N-GQDs showed minimal impact on healthy cells without targeting modifications, significantly improving therapeutic safety.