Making Cells as a “Nirvana Phoenix”: Precise Coupling of Precursors Prior to ROS Bursts for Intracellular Synthesis of Quantum Dots

Rationally coupling natural biochemical reactions for live-cell synthesis of inorganic nanocrystals with fluorescence, such as quantum dots (QDs) especially near-infrared (NIR), holds significant potential for <i>in situ</i> labeling and bioimaging. However, the introduced exogenous reactants and intracellularly produced species, e.g., reactive oxygen species (ROS), often cause cell damage, decreasing the fluorescence of the QDs. Herein, we have found that cell-adaptable selenocystine ((Cys-Se)₂) can be reduced to biocompatible low-valence Se precursors, which could be subsequently hijacked by timely added Ag-glutathione (AgSG) to be transformed into NIR Ag₂Se QDs. Such a comprehensive control strategy can inhibit the production of cytotoxic Se species and ROS bursts, significantly increasing the cell viability from 4 to 80% and enhancing the fluorescence of intracellularly synthesized Ag₂Se QDs by over 8.7 times. Notably, the proliferative and <i>in vivo</i> tumorigenic capacities of the cells with strong NIR fluorescence-emitting functions could be maintained, enabling long-term tracking of cell division and disease progression. This work has provided new insights into fully excavating the potential of cells for the synthesis of inorganic nanocrystals by designing biocompatible precursors and also opened a new window for conventional synthetic biology from organic to inorganic.