Mitochondria‐Targeting Small‐Molecule NIR‐II Fluorescent Probes for Imaging and Treatment of Tumor

Abstract Mitochondrial membrane potential (Δ Ψ m)‐targeting molecular probes play an essential role in diagnosing and treating diseases. Recently, the second near‐infrared window (NIR‐II, 1000–1700 nm) fluorescent imaging has been actively studied as an attractive imaging modality. However, small molecule Δ Ψ m‐targeting NIR‐II probes are rarely reported, especially for highly efficient imaging and treatment of tumors. Herein, a small molecule probe named TQPTPP is designed and synthesized by conjugation of a novel D‐A type dye TQT1009 with Δ Ψ m‐targeting molecule alkyl triphenylphosphine (TPP) through a polyethylene glycol‐8 (PEG 8 ) linker. The conventional ICG dye is also coupled with TPP through PEG 8 to produce ICGTPP as a comparison. TQPTPP showed a fluorescence quantum yield of 0.041% and excellent photothermal conversion efficiency (61.4%). It can be self‐assembled into nanoparticles and still preserve Δ Ψ m‐targeting capability. Tumor imaging is further performed, and results showed a long tumor retention time of TQPTPP (maximum tumor signal on day five and signal‐to‐noise ratio up to nine). As a comparison, ICGTPP remained a single molecule with Δ Ψ m‐targeting capability. But it has shorter tumor retention and lower photostability. These results suggested the novel D‐A small molecule ΔΨ m‐targeting NIR‐II probe TQPTPP provided a new tool for diagnosing and treating tumors.