Visualizing the chronicle of multiple cell fates using a near-IR dual-RNA/DNA–targeting probe
Linawati Sutrisno, Gary J. Richards, Jack D. Evans, Michio Matsumoto, Xianglan Li, Koichiro Uto, Jonathan P. Hill, Masayasu Taki, Shigehiro Yamaguchi, Katsuhiko Ariga
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 ( TEG 8 -N14 ), we unexpectedly achieved discrimination of multiple cell states, including apoptosis, necrosis, necroptosis, and senescence, based on RNA/DNA changes. Specifically, TEG 8 -N14 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.