Suppressing Nonradiative Decay in BF₂ Formazanates via Donor Bromination for Cancer Phototheranostics

Dominant nonradiative decay pathways in second-near-infrared (NIR-II) small-molecule fluorescent dyes critically impair both radiative emission and intersystem crossing (ISC) efficiencies, limiting their utility in fluorescence imaging (FLI) and phototherapy. Herein, we report a donor bromination strategy to suppress nonradiative decay in a boron difluoride (BF₂) formazanate dye BDFTBr for NIR-II FLI-guided tumor photothermal and photodynamic therapy. Compared with the unbrominated analogue BDFTH, BDFTBr with donor bromination maintains a stereoscopic conformation and suppresses intramolecular vibrations, reducing vibrationally induced nonradiative heat dissipation and enhancing the fluorescence quantum yield by ∼3.75-fold. Additionally, donor bromination narrows the singlet-triplet energy gap (ΔE_S-T) and facilitates ISC, leading to the improved generation of multiple reactive oxygen species, even under the hypoxic tumor microenvironment. In vitro and in vivo studies confirm that BDFTBr nanoparticles enable efficient NIR-II FLI-guided tumor ablation with minimal systemic toxicity. This work provides a generalizable strategy for suppressing nonradiative decay in NIR-II small-molecule fluorescent dyes, advancing their potential in multimodal cancer phototheranostics.