LAUSR

Phototheranostics with second near‐infrared (NIR‐II) imaging and photothermal effect have become a burgeoning biotechnology for tumor diagnosis and precise treatment. As important parameters of phototheranostic agents (PTAs), fluorescence quantum yield (QY) and photothermal conversion efficiency (PCE) are usually considered as a pair of contradictions that is difficult to be simultaneously enhanced. Herein, a fluorination strategy for designing A–D–A type PTAs with synchronously improved QY and PCE is proposed. Experimental results show that the molar extinction coefficient (ε), NIR‐II QY, and PCE of all fluorinated PTAs nanoparticles (NPs) are definitely improved compared with the chlorinated counterparts. Theoretical calculation results demonstrate that fluorination can maximize the electrostatic potential difference by virtue of the high electronegativity of fluorine, which may increase intra/intermolecular D–A interactions, tighten molecule packing, and further promote the increase of ε, ultimately leading to simultaneously enhanced QY and PCE. In these PTA NPs, FY6‐NPs display NIR‐II emission extended to 1400 nm with the highest NIR‐II QY (4.2%) and PCE (80%). These features make FY6‐NPs perform well in high‐resolution imaging of vasculature and NIR‐II imaging‐guided photothermal therapy (PTT) of tumors. This study develops a valuable guideline for constructing NIR‐II organic PTAs with high performance.