Transforming Non-Photosensitizing Fluorophores into ROS Photogenerators via Radical-Promoted Intersystem Crossing

• • Guanidinium modification converts non-photosensitizing fluorophores into ROS generators with prolonged triplet lifetimes and considerable ROS production, as evidenced by EPR and HRMS identification of stable radical cations. • • The strategy is general, not limited to specific molecular structures, enabling broad applicability across diverse fluorophore scaffolds. • • In vitro and in vivo experiments demonstrate that guanidinium-modified photosensitizers induce immunogenic cell death (ICD) and elicit potent anti-tumor immunity, achieving significant tumor regression. • • Mechanistic studies reveal that nitrogen-centered radical cations stabilized by p-π conjugation enhance ISC and prolong triplet excited state lifetimes, providing a new design principle for heavy-atom-free photosensitizers.