Permeability-Controlled\nProbe for Ratiometric Detection\nof Plasma Membrane Integrity and Late Apoptosis

The\ndestruction of plasma membrane integrity is closely\nrelated\nto immune response, neuronal injury, cell apoptosis, and other pathological\nevents. However, the construction of ratiometric fluorescent probes\ncapable of detecting plasma membrane integrity remains a significant\nchallenge, hindering in-depth studies on related biomedical areas.\nHerein, a polarity-responsive fluorescent probe was constructed for\nthe ratiometric detection of cell membrane integrity for the first\ntime. The probe targeted intact plasma membranes in healthy cells\nand relocated into the cytoplasm to give significantly red-shifted\nfluorescence after plasma membrane damage. Molecular simulations revealed\nthat the high transmembrane barrier and amphipathic nature of the\nprobe were responsible for its targeting ability. With the probe,\nthe ratiometric detection of late apoptosis stage was realized for\nthe first time, and the membrane damage of tumor cells induced by\nUV irradiation, toxins, and antitumor drugs was visualized. The effect\nof formaldehyde on membrane integrity was evaluated using a probe,\nand cysteine was proved to be a potential detoxifier to counteract\nthe toxicity of formaldehyde.