Simultaneous Induction and Self‐Reporting of Nucleolar Stress by a Nucleolus‐Targeted Platinum(II) Complex via Lifetime Imaging
Abstract
Abstract The nucleolus exhibits characteristic viscous fluid dynamics, whereas nucleolar stress plays a key role in carcinogenesis. However, monitoring nucleolar viscosity in living cells remains a great challenge, which also leads to the lack of a clear report on the relationship between nucleolar viscosity and nucleolar stress. Herein, a nucleolus‐targeted platinum(II) complex with monodentate ligands ( Pt2 ) has been developed, which can rapidly accumulate in the nucleolus and inhibit ribosome biogenesis through energy‐dependent signaling pathways, eventually inducing nucleolar stress and simultaneously monitoring nucleolar viscosity via phosphorescence lifetime imaging (PLIM). The phosphorescence response of Pt2 to viscosity is achieved by suppressing the structural distortion to the non‐emissive d–d excited state and restricting the rotation of Pt─N coordination bonds, which is different from other commonly reported viscosity probes in the literature. After exposure to Pt2 or other antineoplastic agents, which can induce nucleolar stress, the gradual decrease of nucleolar viscosity is observed in living cells in a quantitative and real‐time manner, indicating that nucleolar viscosity can be used as a real‐time monitor of the extent of nucleolar stress. This work reports the first example of a metal complex that can achieve simultaneous induction and self‐reporting of nucleolar stress via PLIM of nucleolar viscosity.
Article Details
Authors (11)
Bin Liu
Jing Yang
Angela Sin‐Yee Law
Institute of Molecular Functional Materials State Key Laboratory of Synthetic Chemistry and Department of Chemistry The University of Hong Kong Pokfulam Road Hong Kong People's Republic of China
Xu‐Xian Su
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry State Key Laboratory of Anti‐Infective Drug Discovery and Development Institute of Green Chemistry and Molecular Engineering Guangdong Basic Research Center of Excellence for Functional Molecular Engineering School of Chemistry Sun Yat‐Sen University Guangzhou 510006 People's Republic of China
Ziyong Chen
Institute of Molecular Functional Materials, State Key Laboratory of Synthetic Chemistry and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, 999077, P. R. China
Ming‐Yi Leung
Institute of Molecular Functional Materials State Key Laboratory of Synthetic Chemistry and Department of Chemistry The University of Hong Kong Pokfulam Road Hong Kong People's Republic of China
Michael Ho‐Yeung Chan
Institute of Molecular Functional Materials State Key Laboratory of Synthetic Chemistry and Department of Chemistry The University of Hong Kong Pokfulam Road Hong Kong People's Republic of China
Eric Ka‐Ho Wong
Institute of Molecular Functional Materials State Key Laboratory of Synthetic Chemistry and Department of Chemistry The University of Hong Kong Pokfulam Road Hong Kong People's Republic of China
Qian Cao
Zong‐Wan Mao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry State Key Laboratory of Anti‐Infective Drug Discovery and Development Institute of Green Chemistry and Molecular Engineering Guangdong Basic Research Center of Excellence for Functional Molecular Engineering School of Chemistry Sun Yat‐Sen University Guangzhou 510006 People's Republic of China
Vivian Wing‐Wah Yam
Institute of Molecular Functional Materials State Key Laboratory of Synthetic Chemistry and Department of Chemistry The University of Hong Kong Pokfulam Road Hong Kong People's Republic of China