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A dual-functional mitochondrial probe for melanoma visualization and PI3K/AKT/mTOR-EMT signaling axis-mediated
Tong Xia1, Hongye Liao1, Ziyuan Zeng1
1Department of Dermatology, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China.
Abstract:
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.
Insights
A new near-infrared (NIR) fluorescent probe, IR-545, effectively targets melanoma cell mitochondria, inhibiting cancer growth and metastasis. This probe shows promise for both imaging and treating melanoma with minimal side effects.
Area of Science:
- Oncology
- Biomedical Imaging
- Molecular Biology
Background:
- Melanoma is a dangerous cancer with limited treatment options.
- Mitochondria are key targets in cancer therapy.
- Near-infrared (NIR) fluorescence probes offer advantages for deep tissue imaging.
Purpose of the Study:
- To develop and evaluate a novel NIR fluorescent probe, IR-545, for melanoma imaging and therapy.
- To investigate the mitochondrial targeting and antitumor mechanisms of IR-545.
Main Methods:
- In vitro studies: melanoma cell uptake via organic anion-transport polypeptides, mitochondrial targeting, apoptosis induction, PI3K/AKT/mTOR pathway and epithelial-mesenchymal transition (EMT) inhibition, proliferation and metastasis suppression.
- In vivo studies: tumor growth inhibition in mice.
- Histological analysis: immunofluorescence, immunohistochemistry, H&E staining.
Main Results:
- IR-545 demonstrated specific uptake and mitochondrial targeting in melanoma cells.
- IR-545 induced apoptosis, inhibited the PI3K/AKT/mTOR pathway and EMT, and suppressed melanoma cell proliferation and metastasis.
- In vivo, IR-545 significantly inhibited tumor growth with no observed side effects.
Conclusions:
- IR-545 is a novel NIR fluorescent probe with dual potential for melanoma imaging and therapy.
- IR-545 targets mitochondria, induces apoptosis, and inhibits melanoma progression.
- IR-545 represents a promising new approach for melanoma treatment.

