One-for-All Phototheranostic Agent Based on Aggregation-Induced Emission Characteristics for Multimodal Imaging-Guided Synergistic Photodynamic/Photothermal Cancer Therapy

Phototheranostics represents a promising direction for modern precision medicine, which has recently received considerable attention for cancer research. The ingenious integration of all phototheranostic modalities in a single molecule with precise spatial colocalization is a tremendously challenging task, which mainly arises from the complexity of molecular design and energy dissipation. Reports on a single molecular one-for-all theranostic agent are still very rare. Herein, we designed two novel aggregation-induced emission (AIE)-active fluorogens (AIEgens, named DPMD and TPMD) with a cross-shaped donor-acceptor structure via a facile synthetic method and constructed versatile nanoparticles (NPs) by encapsulating AIEgen with an amphiphilic polymer. The AIEgen TPMD with a twisted structure, high donor-acceptor (D-A) strength, small singlet-triplet energy gap, and abundant intramolecular rotators and vibrators was selected as an ideal candidate for balancing and utilizing the radiative and nonradiative energy dissipations. Notably, TPMD NPs simultaneously possess adequate near-infrared (NIR) fluorescence emission at 821 nm for fluorescence imaging, effective reactive oxygen species generation for photodynamic therapy (PDT), and outstanding photothermal effect for photoacoustic imaging, photothermal imaging, and photothermal therapy (PTT), which demonstrates the superior potential of AIE NPs in multimodal imaging-guided synergistic PDT/PTT therapy.