Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, 117585, Singapore, Singapore.
Angew Chem Int Ed Engl. 2019 Nov 4;58(45):16229-16235. doi: 10.1002/anie.201906099. Epub 2019 Sep 30.
The detection and elimination of intracellular bacteria remain a major challenge. In this work, we report an aggregation-induced emission (AIE) bioprobe that can detect bacterial infection and kill bacteria surviving inside macrophages through a dynamic process, notably specific molecular tailoring of the probe by caspase-1 activation in infected macrophages and accumulation of the residue on phagosomes containing bacteria, leading to light-up fluorescent signals. Moreover, the AIEgen can serve as a photosensitizer for generation of reactive oxygen species (ROS); and the average ROS indicator fluorescent signal intensity per unit area in the bacterial phagosomes is approximately 2.7-fold higher than that in the cytoplasm. This, in turn, induces bacteria killing with high efficiency and minimal cytotoxicity towards macrophages. We envision that this specific light-up bioprobe may provide a new approach for selective and sensitive detection and eradication of intracellular bacterial infections.
胞内细菌的检测和清除仍然是一个主要挑战。在这项工作中，我们报告了一种聚集诱导发射（AIE）生物探针，它可以通过一个动态过程来检测细菌感染，并杀死存活在巨噬细胞内的细菌，特别是通过感染巨噬细胞中 caspase-1 的激活和在含有细菌的吞噬体上聚集残留物来对探针进行特异性分子修饰，从而导致荧光信号的点亮。此外，AIEgen 可以用作产生活性氧（ROS）的光敏剂；并且细菌吞噬体中单位面积的平均 ROS 指示剂荧光信号强度大约比细胞质中的高 2.7 倍。这反过来又以高效率诱导细菌杀伤，并且对巨噬细胞的细胞毒性最小。我们设想，这种特异性点亮生物探针可能为选择性和敏感地检测和消除细胞内细菌感染提供一种新方法。
