Water-Soluble NIR-II Photothermal Agent for Sprayable Skin Cancer Therapy

Skin cancer therapy demands noninvasive approaches to overcome current treatments' limitations, and second near-infrared window (NIR-II) photothermal agents offer potential solutions with deep tissue penetration and high efficiency. However, limitations in water solubility and photothermal efficiency restrict their broader application. Here, through rational molecular engineering of the indocyanine green (ICG) scaffold, we developed WCY11 via strategic π-conjugation extension and multisulfonic acid functionalization. This dual-strategy yielded complete aqueous solubility while conferring exceptional photophysical properties: strong NIR-II absorption (980 nm), record-high photothermal conversion efficiency (65.6%), and substantial fluorescence quantum yield (5.05%). Importantly, WCY11's compatibility with spray-based topical administration represents a paradigm shift in photothermal therapeutics. This delivery approach enables precise tumor targeting while avoiding systemic exposure and toxicity risks. Comprehensive evaluation demonstrated WCY11's superior therapeutic efficacy in tumor ablation under NIR-II irradiation, effectively addressing the challenges of solubility, performance, and clinical practicality in photothermal therapy.