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.