Simultaneous Induction and Self‐Reporting of Nucleolar Stress by a Nucleolus‐Targeted Platinum(II) Complex via Lifetime Imaging

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.