Multimodal phototheranostics combines multi-dimensional optical imaging with light-activated therapy, offering a promising approach for precise cancer treatment. A major hurdle is creating long-wavelength organic molecules that can concurrently support multiple second near-infrared window (NIR-II) imaging modalities and synergistic phototherapy. Herein, we report a novel donor-acceptor-donor (D-A-D) structured squaraine dye (SQ8), rationally designed and selected via preliminary DFT calculations owing to its narrow bandgap and red-shifted optical properties. Notably, SQ8 spontaneously self-assembles into ordered J-aggregates in aqueous media, yielding an exceptionally red-shifted emission at 1281 nm. This ultra-long NIR-II fluorescence enables high-contrast deep-tissue imaging with superior signal-to-background ratio and spatial resolution. After co-assembly with DSPE-PEG2000, the formed nanoparticles (SQ8@NPs) display excellent water stability, a high photoluminescence quantum yield (PLQY = 0.842%), and a remarkable photothermal conversion efficiency (PCE = 43.3%) under 1064 nm laser irradiation. Leveraging these synergistic properties, SQ8@NPs achieve dual-modal NIR-II fluorescence and photoacoustic imaging (FLI/PAI) and effective light-triggered tumor ablation both in vitro and in vivo. This work not only expands the family of ultra-long wavelength organic fluorophores but also provides a robust paradigm for developing image-guided photothermal therapy (PTT) platforms for deep-seated tumors.
Zhou et al. (Thu,) studied this question.