Advanced Research Institute of Multidisciplinary Science, Beijing Institute of Technology, Beijing 100081, China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China.
Anal Chem. 2022 Mar 8;94(9):3840-3848. doi: 10.1021/acs.analchem.1c04741. Epub 2022 Feb 18.
Reconstituting and probing exosome-cell interactions is critical for elucidating exosome-related cell biology and advancing their diagnostic and therapeutic potential. We report here an exosomal engineering strategy to achieve controlled regulation of exosome-cell interactions with activatable sensing capability. The approach relies on membrane-protein directed, programmable DNA self-assembly to construct a DNA polymeric scaffold with multivalent display of structure-switchable aptamer sensing probes on exosome surfaces. The engineered exosomes exhibit enhanced cancer cell targeting ability compared to exosomes modified with monovalent aptamers. Furthermore, the anchored aptamer probes could be activated by specific membrane protein targeting, followed by structural switching to report an output fluorescence signal, thus allowing dynamic monitoring of exosome-cell interactions both in vitro and in vivo. We envision this will provide a complementary tool for specific regulation and monitoring of exosome-cell docking interactions and will advance the development of exosome-based biomedical applications.
重建和探测外泌体-细胞相互作用对于阐明外泌体相关的细胞生物学并推进其诊断和治疗潜力至关重要。我们在这里报告了一种外泌体工程策略，以实现对外泌体-细胞相互作用的可控调节，同时具有激活感应能力。该方法依赖于膜蛋白导向的可编程 DNA 自组装，在多价展示结构可切换适体感应探针的外泌体表面构建 DNA 聚合支架。与用单价适体修饰的外泌体相比，工程化的外泌体表现出增强的癌细胞靶向能力。此外，锚定的适体探针可以通过特定的膜蛋白靶向进行激活，随后进行结构切换以报告输出荧光信号，从而可以在体外和体内动态监测外泌体-细胞相互作用。我们设想这将为外泌体-细胞对接相互作用的特异性调节和监测提供一种补充工具，并将推进基于外泌体的生物医学应用的发展。
