Tetrazine-derived chromones as conditionally activated solvatochromic fluorescent probes for dual imaging of lipid droplets and mitochondria

Abstract

Lipid droplets (LDs) are crucial organelles that play important roles in various physiological and pathological processes. The LD–mitochondria interplay is pivotal for cellular energy metabolism and lipid homeostasis. It is thus vital to develop high-performance LD–mitochondria dual imaging probes for studying their biological functions. Herein, we reported a new class of conditionally activated fluorogenic probes based on the conjugation of chromone and tetrazine. These probes could be either photoactivated to generate photostable and solvatochromic photoproducts for visualizing LDs and real-time, in situ monitoring of ferroptosis-induced LD dynamics with a high level of spatiotemporal control or bioorthogonally activated for mitochondria-specific imaging based on a pre-targeted approach. Most importantly, this strategy was successfully applied to label LDs and mitochondria simultaneously and realized two-color imaging in the lambda mode, which showed the great potential of using fluorescence imaging to explore the functions of LDs and related organelles.