Intrinsic Mitochondrial Reactive Oxygen Species (ROS) Activate the In Situ Synthesis of Trimethine Cyanines in Cancer Cells
Hao Heng, Gang Song, Xuetong Cai, Jian Sun, Ke Du, Xiaoran Zhang, Xia Wang, Fude Feng, Shu Wang
Abstract
Environment-responsive in situ synthesis of molecular fluorescent dyes is challenging. Herein, we develop a photoextension strategy to make trimethine cyanines with decent conversion efficiency (up to 81 %) using 1-butyl 2,3,3-trimethyl 3H-indole derivatives as the sole precursors, and demonstrate a free radical mechanism. In the inducer-extension stage, free radicals and reactive oxygen species (ROS) were able to mediate similar reactions with no assistance of light. We explored a Mito-extension strategy to in situ synthesize trimethine cyanines in the living cells. The cellular ROS-dependence provided a foundation for preferential cyanine expression in cancer cells. Finally, we applied an iodized precursor as an intrinsic ROS-activated theranostic agent that integrated mitochondria-targeted cyanine synthesis, cell imaging and phototherapy.