Precise Modulation of Excited‐State Energy Flow via Consecutive Twisted Intramolecular Charge Transfer (ConTICT) for Autophagy‐Blocking Photothermal Therapy

ABSTRACT The efficacy of photothermal therapy is fundamentally governed by the efficiency of non‐radiative decay; however, current organic photothermal agents are severely limited by competitive energy flow pathways and sluggish excited‐state decay kinetics. These dual bottlenecks prevent the maximization of heat generation per absorbed photon. To overcome these barriers, we designed energy barriers that divert energy from both radiative decay and triplet‐state transfer toward non‐radiative heat generation, thereby enhancing efficiency. Furthermore, by employing a consecutive twisted intramolecular charge transfer (ConTICT) mechanism, we accelerate the cycle rate of non‐radiative relaxation. The long‐wavelength, high‐efficiency photothermal molecule Cy‐CF 3 undergoes ConTICT cycling 112 times per 10 ns, achieving a multiple photothermal cycle efficiency of 66.8%, thus addressing the challenge of slow return to the ground state. This holistic design strategy enables Cy‐CF 3 to achieve a high photothermal conversion efficiency of 87.4% under low‐power irradiation (300 mW cm −2 ). Furthermore, it induces disruption of lysosomal structures, and blocks autophagy processes. Upon encapsulation into liposomes, the photothermal agent exhibits specific tumor site targeting, enables fluorescence/photothermal/photoacoustic trimodal deep‐tissue imaging, and delivers robust in vivo antitumor therapeutic efficacy. This work presents a generalizable molecular strategy for precisely manipulating quantum energy flow to construct next‐generation phototheranostics.