Dissecting Exciton Dynamics in pH‐Activatable Long‐Wavelength Photosensitizers for Traceable Photodynamic Therapy

Abstract

Tumor‐specific activatable long‐wavelength (LW) photosensitizers (PSs) show promise in overcoming the limitations of traditional photodynamic therapy (PDT), such as systemic phototoxicity and shallow tissue penetration. However, their insufficient LW light absorption and low singlet oxygen quantum yield (F1O2) usually require high laser power density to produce thermal energy and synergistically enhance PDT. The strong photothermal radiation causing acute pain significantly reduces patient compliance and hinders the broader clinical application of LW PDT. Through the exciton dynamics dissection strategy, we have developed a series of pH‐activatable cyanine‐based LW PSs (LET‐R, R = H, Cl, Br, I), among which the activated LET‐I exhibits strong light absorption at 808 nm and a remarkable 3.2‐fold enhancement in F1O2 compared to indocyanine green. Transient spectroscopic analysis and theoretical calculations confirmed its significantly promoted intersystem crossing and simultaneously enhanced LW fluorescence emission characteristics. These features enable the activatable fluorescence and photoacoustic dual‐modal imaging‐escorted complete photodynamic eradication of tumors by the folic acid (FA)‐modified LET‐I probe (LET‐I‐FA), under the ultralow 808 nm laser power density (0.2 W cm‐2) for irradiation, without the need for photothermal energy synergy. This research presents a novel strategy of dissecting exciton dynamics to screen activatable LW PSs for traceable PDT.