Unlocking Long‐Lived Charge‐Separated State in Pentamethine Cyanine Based on Anionic Hofmeister Effect for Photodynamic Immunotherapy

The trade‐off between fluorescence imaging and photosensitization capability of pentamethine cyanine (Cy5) has greatly impeded its applications in phototherapy. Molecular design strategy has been the prevailing way to enhance its ROS generation efficiency, yet still unsatisfactory in the synergistic optimization of the synthesis procedure and the charge separation (CS) efficiency. Herein, by the incorporation of the stereo‐π anion BPh 4 − into a series of Cy5 skeletons, the ROS generation capability was enhanced by 8 times, and an efficient oxygen‐independent electron transfer pathway was evoked, unlocking the long‐lived charge‐separated state (CSs) and favoring photodynamic immunotherapy. The “End to End” stacked Cy5‐BPh 4 ensured weak electronic coupling (V) and a higher driving force for blocking charge recombination (CR), ultimately unfolding its efficient CS to facilitate subsequent electron transfer pathways. The superior ROS production in Cy5‐BPh 4 conferred potent phototoxicity against hypoxic cancer cells and elicited immunogenic cell death responses, achieving excellent antitumor efficacy in both primary and distant tumors. Overall, this work delivered a universal paradigm to endow cyanine‐PSs with long‐lived CSs for antitumor photodynamic immunotherapy.