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

Mitochondrial membrane potential (& UDelta;& psi;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 & UDelta;& psi;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 & UDelta;& psi;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 & UDelta;& psi;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 & UDelta;& psi;m-targeting capability. But it has shorter tumor retention and lower photostability. These results suggested the novel D-A small molecule & UDelta;& psi;m-targeting NIR-II probe TQPTPP provided a new tool for diagnosing and treating tumors.