A novel NIR fluorescent probe inhibits melanoma progression through apoptosis and ERK/DRP1-mediated mitochondrial fission.

[Display omitted] • IR-418, a newly designed hemicyanine-based NIR fluorescent probe, demonstrated effective targeting of melanoma cell mitochondria for NIR imaging. • IR-418′s inhibition of melanoma growth through the promotion of mitochondrial apoptosis (Bax/Bcl-2/Cleaved Caspase pathway). • IR-418 inhibited melanoma metastasis by inhibiting mitochondrial fission through the ERK/DRP1 pathway. Melanoma, a highly metastatic malignant tumour, necessitated early detection and intervention. This study focuses on a hemicyanine fluorescent probe activated by near-infrared (NIR) light for bioimaging and targeted mitochondrial action in melanoma cells. IR-418, our newly designed hemicyanine-based NIR fluorescent probe, demonstrated effective targeting of melanoma cell mitochondria for NIR imaging. In vitro and in vivo experiments revealed IR-418′s inhibition of melanoma growth through the promotion of mitochondrial apoptosis (Bax/Bcl-2/Cleaved Caspase pathway). Moreover, IR-418 inhibited melanoma metastasis by inhibiting mitochondrial fission through the ERK/DRP1 pathway. Notably, IR-418 mitigated abnormal ATL and ASL elevations caused by tumours without inflicting significant organ damage, indicating its high biocompatibility. In conclusion, IR-418, a novel hemicyanine-based NIR fluorescent probe targeting the mitochondria, exhibits significant fluorescence imaging capability, anti-melanoma proliferation, anti-melanoma lung metastasis activities and high biosafety. Therefore, it has significant potential in the early diagnosis and treatment of melanoma. [ABSTRACT FROM AUTHOR]