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.