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Aliphatic Group-Tethered Iridium Complex as a Theranostic Agent against Malignant Melanoma Metastasis
journal contribution
posted on 2020-03-26, 21:13 authored by Ke-Jia Wu, Shih-Hsin Ho, Jia-Yi Dong, Ling Fu, Shuang-Peng Wang, Hao Liu, Chun Wu, Chung-Hang Leung, Hui-Min David Wang, Dik-Lung MaMalignant
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.