Metabolism‐Driven Disassembly of Nanoprobes for Bacterial Detection, Imaging, and Photo‐Inactivation

Abstract Bacterial infections have posed a grave challenge to public health. Molecular fluorescent probes play increasing important roles in diagnosis and treatment of bacterial infections, but are frequently hindered by the aggregation‐caused quenching and low bacterial specificity as well as reduced bactericidal activity. Herein, metabolism‐driven nanoprobes (HF‐D‐Ala NPs) are reported for bacteria‐activated detection and following visible‐light induced inactivation. The nanoprobes are formed via facile self‐assembly of amphiphilic fluorescent small molecule (HF‐D‐Ala), showing strongly quenched fluorescence and enhanced photostability due to the dense aggregation of hydrophobic structural units. Once encountering with bacteria, HF‐D‐Ala NPs are disassembled into free HF‐D‐Ala, which can be further integrated into cell walls via bacterial metabolism. This progress can readily “turn‐on” the molecular fluorescence, realizing visual bacterial detection and imaging. Subsequently, the labeled bacteria can be effectively inactivated by carbon monoxide released from incorporated HF‐D‐Ala upon visible‐light. With good specificity and biocompatibility, HF‐D‐Ala NPs can selectively detect and inactivate bacteria in biofilms and bacteria co‐existing with mammalian cells, showing great potential for bacterial infection theranostic applications.