Chemically engineered exogenous organic reactions in living cells for in situ fluorescence imaging and biomedical applications

The unique microenvironment within living cells, characterized by high glutathione levels, reactive oxygen species concentrations, and active enzymes, facilitates the execution of chemical reactions. Recent advances in organic chemistry and chemical biology have leveraged living cells as reactors for chemical synthesis. This review summarizes recent reports on key intracellular in situ synthesis processes, including the synthesis of near-infrared fluorescent dyes, intracellular oxidative cross-linking, bioorthogonal reactions, and intracellular polymerization reactions. These methods have been applied to fluorescence imaging, tumor treatment, and the enhancement of biological functions. Finally, we discuss the challenges and opportunities in the field of in situ intracellular synthesis. We aim to guide the design of chemical molecules for in situ synthesis, improving the efficiency and control of artificial reactions in living cells, and ultimately achieving cell factory-like exogenous biological synthesis, biological function enhancement, and biomedical applications.