Bio‐orthogonal AIE Dots Based on Polyyne‐Bridged Red‐emissive AIEgen for Tumor Metabolic Labeling and Targeted Imaging

In this work, we aim to develop cancer cell‐targeting AIE dots based on a polyyne‐bridged red‐emissive AIEgen, 2TPE‐4E, through the combination of metabolic engineering and bio‐orthogonal reactions. Azide groups on a tumor were efficiently produced by intravenous injection of Ac4ManNAz and glycol‐metabolic engineering. These bio‐orthogonal azide groups could facilitate the specific targeting of DBCO‐AIE dots to the tumor cells undergoing metal‐free click reaction in vivo. The efficiency of this targeting strategy could be further improved with the development of new bio‐orthogonal chemical groups with higher reactivity and a large amount of AIEgens could be delivered to the tumor for diagnosis. Bridging the gap: Bio‐orthogonal red‐emissive AIE dots based on the polyyne‐bridged AIEgen were fabricated through the nanoprecipitation method using DBCO‐decorated PEG‐lipids as encapsulation matrices. Furthermore, a two‐step in vivo metabolic enhanced labeling strategy for in vivo cancer‐targeting delivery was developed. Various hydrophobic AIEgens can be delivered to disease areas with abnormal metabolic processes.