NIR‐II Emissive Ru(II) Metallacycle Assisting Fluorescence Imaging and Cancer Therapy

Abstract Despite the success of emissive Ruthenium (Ru) agents in biomedicine, problems such as the visible‐light excitation/emission and single chemo‐ or phototherapy modality still hamper their applications in deep‐tissue imaging and efficient cancer therapy. Herein, an second nearinfrared window (NIR‐II) emissive Ru(II) metallacycle (Ru1000, λ em = 1000 nm) via coordination‐driven self‐assembly is reported, which holds remarkable deep‐tissue imaging capability (≈6 mm) and satisfactory chemo‐phototherapeutic performance. In vitro results indicate Ru1000 displays promising cellular uptake, good cancer‐cell selectivity, attractive anti‐metastasis properties, and remarkable anticancer activity against various cancer cells, including cisplatin‐resistant A549 cells (IC 50 = 3.4 × 10 −6 m vs 92.8 × 10 −6 m for cisplatin). The antitumor mechanism could be attributed to Ru1000‐induced lysosomal membrane damage and mitochondrial‐mediated apoptotic cell death. Furthermore, Ru1000 also allows the high‐performance in vivo NIR‐II fluorescence imaging‐guided chemo‐phototherapy against A549 tumors. This work may provide a paradigm for the development of long‐wavelength emissive metallacycle‐based agents for future biomedicine.