Engineering Nanoemulsions to Maximize NIR‐II Fluorescence and Preserve Photothermal Performance of a Novel Boron Difluoride Formazanate Dye

Abstract

ABSTRACT 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.