π-Bridge engineering strategy: tailoring S-xanthene dyes with strong absorption for high-efficiency photothermal therapy.

NIR-II probes show great potential for fluorescence imaging (FLI) and therapeutics, where the molar extinction coefficient (MEC), a pivotal optical parameter, governs their imaging quality and therapeutic efficacy. Nevertheless, engineering NIR-II probes with ultrahigh MEC remains a formidable challenge, limiting their biomedical applications. In this work, we designed a superior NIR-II D-π-A-π-D probe, SCU-SX-T, which features an S-xanthene core as the conjugate acceptor, a diphenylamine (DPA) rotor, and π-bridge that induces bathochromic shifts in absorption/emission spectra while enhancing molecular rigidity and planarity. This rational molecular design enables the probe to achieve exceptionally ultrahigh MEC of 2.0 × 10⁵ M^-1 cm^-1, outstanding photothermal conversion efficiency (PCE) of 91.5%, and fluorescence quantum yield of 0.04%. Notably, the SCU-SX-T NPs facilitated high-resolution vascular imaging of the abdominal region and precise surgery in living mice, demonstrating their robust NIR-II fluorescence capability. Furthermore, NIR-II FLI/photothermal imaging (PTI)-guided tumor visualization and photothermal therapy (PTT) was successfully achieved. The integration of α-PD-L1 checkpoint blockade therapy led to significant inhibition of proximal tumor growth, highlighting the potential of this synergistic therapeutic strategy. Overall, this work provides a comprehensive NIR-II probe with excellent performance and ideas for the future design of NIR-II probes with high MEC.