J‐Aggregation‐Induced Ultra‐Long 1281 nm NIR‐II Multimodal Imaging of a Narrow‐Bandgap Squaraine for Photothermal Therapy Guidance

ABSTRACT 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‐PEG ₂₀₀₀ , 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.