Visualizing the Chronicle of Multiple Cell Fate using a Near-IR Dual-RNA/DNA-Targeting Probe

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 UV-vis-sensitive cells. Here, we introduce a method to simultaneously detect variations in RNA and DNA under near-infrared photoexcitation. Utilizing a pyrazinacene-based probe (TEG8-N14), we unexpectedly achieved discrimination of multiple cell states, including apoptosis, necrosis, necroptosis, and senescence, based on RNA-DNA changes. Specifically, TEG8-N14 selectively stains necrotic cells in live samples, while after fixation, it allows detection of ultra-early senescence in UV-vis-sensitive cells, providing approximately two-fold 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.