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

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, λem = 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 (IC50 = 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. Herein, an second nearinfrared window (NIR‐II) emissive Ruthenium (Ru) metallacycle (Ru1000) that holds excellent deep‐tissue penetration capability and satisfactory chemo‐phototherapeutic performance is reported. Ru1100 exhibits promising broad‐spectrum anticancer activity in vitro. Moreover, Ru1100 also allows for in vivo high‐performance fluorescence imaging‐guided precise chemo‐phototherapy in A549 tumor models. These findings provide a paradigm for the development of long‐wavelength emissive metal‐based theranostic agents.