A hydrophilic lysosome-nucleolus immigration fluorescent probe for tracking normal cells from apoptosis to necrosis

Apoptosis and necrosis are two closely related and independent critical biological processes of cells. Their state transitions are closely related to the in vivo microenvironment and are a cutting-edge target for the research of drugs. However, the discriminative visualization of apoptosis to necrosis is an essential and challenging task, and almost no single-molecule probes can discriminatively track this process in detail. Herein, a hydrophilic and organelle-immigrated fluorescent probe (PPCN) with large Stokes shifts was designed for real-time tracking of normal cells from apoptosis to necrosis. Due to its excellent hydrophilicity, PPCN can't be taken up by normal cells; while can light up the lysosomes when apoptosis occurs with the cell membrane permeability increases. Thanks to the multipositive nature of the probe, PPCN can be captured by nucleic acids. Therefore, after lysosomes are damaged, PPCN can further migrate from lysosomes to the nucleolus and report the cell process from apoptosis to necrosis. Thus, three states (normal, apoptosis, and necrosis) of cells were discriminatively visualized according to the localization of PPCN in fluorescence images. Consequently, PPCN can be an essential molecular tool for discriminatively tracking from apoptosis to necrosis in cell biology and medical research.