A dual-functional mitochondrial probe for melanoma visualization and PI3K/AKT/mTOR-EMT signaling axis-mediated antitumor therapy.

Melanoma is a highly metastatic cancer with poor treatment outcomes. Mitochondria, regulated by various signaling pathways, are an important target in cancer therapy. Near-infrared (NIR) fluorescence probes have gained interest due to their properties such as deep tissue penetration, high image sensitivity, and precision targeting. In this study, we developed a novel NIR fluorescent probe IR-545 for melanoma imaging, which demonstrated mitochondrial targeting and antitumor activity in melanoma cells. In vitro experiments showed that IR-545 was taken up by melanoma cells through organic anion-transport polypeptides and targeted tumor cell mitochondria. IR-545 induced apoptosis by inhibiting the PI3K/AKT/mTOR pathway and epithelial-mesenchymal transition (EMT) and suppressed the proliferation and metastasis of melanoma cells. In vivo, IR-545 significantly inhibited tumor growth in BALB/c nude mice. Immunofluorescence, immunohistochemistry, and H&E staining confirmed that IR-545 induced tumor cell apoptosis and inhibited proliferation without notable side effects. In conclusion, IR-545 shows significant potential in imaging and treating melanoma, offering a promising new therapeutic approach.