Symmetrically Fluorinated D‐π‐A Structured Cyanine Dye for Highly Efficient NIR‐II Imaging‐Guided Cancer Phototheranostics

Abstract Near‐infrared‐II (NIR‐II) fluorescence imaging‐guided photothermal therapy (PTT) represents a cutting‐edge approach for precise tumor diagnosis and treatment, providing real‐time therapeutic efficacy evaluation. However, a significant challenge lies in the creation of phototheranostic agents that provide robust imaging and efficient photothermal conversion. To address this, a donor‐ π ‐acceptor (D‐ π ‐A) structure heptamethine cyanine derivative, IR1116, that confers a strong intramolecular charge transfer effect is developed. To enhance its applicability, IR1116 is formulated with DSPE‐PEG to create a water‐dispersible NIR‐II phototheranostic nanoheater, NP _IR1116 . This nanoheater benefits from the incorporation of an electron‐withdrawing group, leading to reduced photooxidation activity and significantly improved photostability. NP _IR1116 exhibits strong NIR‐II absorption and fluorescence, peaking at 1004 and 1116 nm, respectively, as well as a photothermal conversion efficiency of 79% under 1064 nm lasers. In vitro and in vivo studies showed the efficacy of NP _IR1116 in tumor imaging via NIR‐II fluorescence and its ability to effectively induce tumor cell apoptosis under 1064 nm laser irradiation. These findings underscore the potential of NP _IR1116 in NIR‐II fluorescence imaging‐guided PTT for tumor treatment, paving the way for further advancements in NIR‐II dye development and bioimaging technologies.