Molecular Tailoring Based on Forster Resonance Energy Transfer for Initiating Two-Photon Theranostics with Amplified Reactive Oxygen Species.

The fabrication of multifunctional photosensitizers (PSs) with abundant Type I/II ROS for efficient theranostics in the "therapeutic window" (700-900 nm) is an appealing yet significantly challenging task. We herein report a molecular tailoring strategy based on intramolecular two-photon Forster Resonance Energy Transfer (TP-FRET) to obtain a novel theranostic agent (), featuring the amplified advantage of energy donor () and acceptor (), because of the reuse of fluorescence energy with high efficiency of FRET (∼83%). Importantly, under the excitation by the near-infrared (840 nm) window, can not only penetrate the deeper tissue with a higher resolution for fluorescence imaging due to the nonlinear optical (NLO) nature, but also generate more Type I (superoxide anion) and Type II (singlet oxygen) reactive oxygen species for hypoxic PDT. Moreover, targeting lysosomes further promotes the effect of treatment. The experiments and also verify that the developed TP-FRET PS is conducive to treating deep hypoxic tumors. This strategy provides new and significant insights into the design and fabrication of advanced multifunctional PSs.