Aliphatic Group-Tethered Iridium Complex as a Theranostic Agent against Malignant Melanoma Metastasis.

ABSTRACT

Malignant melanoma is a very aggressive form of skin cancer, with a low long-term survival rate. Developing multifunctional theranostic agents to simultaneously track and inhibit the activity of tumor targets is a potential strategy for combating melanoma metastasis. S100B expression is directly correlated with the degree of malignant metastatic melanoma and is overexpressed in the majority of malignant melanoma patients. Herein, the Ir(III) complex 7 was identified as a potent theranostic agent with nanomolar potency against S100B and selectivity over related substrates. Complex 7 exhibited desirable photophysical properties including a large Stokes shift and high photostability, while its long emission lifetime enabled its luminescence signal to be discriminated from a highly autofluorescent background by use of time-resolved emission spectroscopy. Importantly, complex 7 showed strong colocalization with S100B protein in melanoma cells with a stable signal up to at least 12 h, revealing its potential as a cellular probe for S100B. Moreover, complex 7 impeded the interaction between S100B and the C-terminus of p53 in the cytoplasm, thereby restoring the binding of p53 to its target promoters. Finally, complex 7 suppressed tumor growth and restrained lung metastases in vivo in two separate melanoma mouse models. To our knowledge, complex 7 is the first reported theranostic agent for simultaneously monitoring S100B and suppressing malignant melanoma metastasis in vivo via targeting S100B protein.