Visualizing the chronicle of multiple cell fates using a near-IR dual-RNA/DNA-targeting probe.

Sutrisno, Linawati; Richards, Gary J; Evans, Jack D; Matsumoto, Michio; Li, Xianglan; Uto, Koichiro; Hill, Jonathan P; Taki, Masayasu et al. · Sci Adv · 2025

basic_science · Level V

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Abstract

Early detection and late-stage cell fate assessment are key factors to develop therapeutic strategies, although current methods cannot capture early responses or distinguish multiple injury states, especially in ultraviolet-visible (UV-vis)-sensitive cells. Here, we introduce a method to simultaneously detect variations in RNA and DNA under near-infrared photoexcitation. Using a pyrazinacene-based probe (<b>TEG</b><sub><b>8</b></sub><b>-N14</b>), we unexpectedly achieved discrimination of multiple cell states, including apoptosis, necrosis, necroptosis, and senescence, based on RNA/DNA changes. Specifically, <b>TEG</b><sub><b>8</b></sub><b>-N14</b> selectively stains necrotic cells in live samples, while after fixation, it allows detection of ultraearly senescence in UV-vis-sensitive cells, providing approximately twofold greater informational content than existing RNA or DNA fluorophores. These findings break current imaging barriers by enabling comprehensive visualization of single-cell fate histories without being affected by UV-vis or genetic manipulation.

Medical subject headings