Boron difluoride formazanate (BDF) dyes possess intrinsic NIR-I absorption and NIR-II photoluminescence. However, their hydrophobic nature often leads to fluorescence quenching in polar aqueous environment, limiting their performance in biological applications. Here, we report a newly synthesized BDF dye (3) formulated as an oil-in-water nanoemulsion (BDF-NE) that overcomes this challenge by providing a nonpolar oil core microenvironment that closely matches the favorable conditions required to preserve the bright emission of 3. Molecular solubilization of 3 within a glyceryl trioctanoate core, stabilized by a phospholipid/PEG-lipid shell, maintains strong NIR absorption and a high molar extinction coefficient while simultaneously maximizing NIR-II emission intensity. BDF-NE achieves a photothermal conversion efficiency of 66.8%, generates strong photoacoustic (PA) contrast at 780 nm, and exhibits bright NIR-II fluorescence extending beyond 1250 nm with an absolute quantum yield of 2.9%, enabling high-resolution vascular imaging and real-time tracking of tumor accumulation in vivo. In subcutaneous tumor-bearing mice, dual-modal NIR-II/PA imaging-guided photothermal therapy achieves complete ablation of tumors in a subset of mice and significantly prolongs recurrence-free survival without detectable systemic toxicity. This nanoemulsion-based strategy unlocks the full dual-modal theranostic potential inherent to BDF dyes and offers a generalizable strategy for translating hydrophobic NIR fluorophores into high-performance theranostic agents.
Kwon et al. (Mon,) studied this question.