Bioorthogonal In Situ Formation of AIE Luminogens for Imaging Disease Progression via Sigmoidal Signal Amplification
Abstract
AbstractAggregation‐induced emission (AIE) luminogens are promising tools for biological imaging, yet their utility is often limited by nonspecific aggregation and elevated background fluorescence. Here, we present a bioorthogonal in situ formation strategy that enables precise, organelle‐specific activation of AIEgens within live cells. This system employs a dual‐lock mechanism—combining tetrazine quenching and twisted intramolecular charge shuttle (TICS) dynamics—to maintain an ultra‐low fluorescence background in the precursor state, even under aggregating conditions. Upon bioorthogonal reactions and molecular aggregation, the resulting AIEgens exhibit tunable emission peaks ranging from 605 to 665 nm, large Stokes shifts (up to 201 nm), and an exceptional fluorescence enhancement (up to 1033‐fold). Their high biocompatibility and spatial precision allow for multiplexed, simultaneous labeling of intracellular targets. Compared to conventional fluorogenic and bioorthogonal probes, these AIEgens exhibit a sigmoidal amplification response, enabling the sensitive discrimination of subtle biomarker expression differences and the effective identification of injured cells during disease progression. This strategy significantly enhances the specificity and sensitivity of live‐cell imaging, expands the functional utility of AIE luminogens, and offers a versatile platform for high‐resolution, multiplexed bioimaging in biomedical research and diagnostics.
Article Details
Authors (13)
Xinyu Yu
Future Battery Research Center, Global Institute of Future Technology
Xirui Liu
Ningbo Institute of Materials Technology and Engineering
Hongbao Sun
Department of Radiology and Huaxi MR Research Center (HMRRC), Frontiers Science Center for Disease‐Related Molecular Network, State Key Laboratory of Biotherapy West China Hospital, Sichuan University Huaxi Research Building, 001 4th Keyuan Road Chengdu 610041 China
Tianruo Shen
National Supercomputer Center in Tianjin
Yingqiao Deng
Department of Radiology and Huaxi MR Research Center (HMRRC), Frontiers Science Center for Disease‐Related Molecular Network, State Key Laboratory of Biotherapy West China Hospital, Sichuan University Huaxi Research Building, 001 4th Keyuan Road Chengdu 610041 China
Haiyan Ren
Peixuan Zou
Department of Biopharmaceutics West China School of Pharmacy, Sichuan University No. 17 People's South Road Chengdu 610041 China
Yongxiang Zheng
Department of Biopharmaceutics West China School of Pharmacy, Sichuan University No. 17 People's South Road Chengdu 610041 China
Peihong Xiao
Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, School of Medicine University of Electronic Science and Technology of China 32 West Section 2, First Ring Road Chengdu 610072 China
Qiyong Gong
Department of Radiology, Huaxi MR Research Center, Institute of Radiology and Medical Imaging, West China Hospital of Sichuan University
Meng Qin
Xiaogang Liu
Haoxing Wu
Department of Radiology and Huaxi MR Research Center (HMRRC), Frontiers Science Center for Disease‐Related Molecular Network, State Key Laboratory of Biotherapy West China Hospital, Sichuan University Huaxi Research Building, 001 4th Keyuan Road Chengdu 610041 China