Multivalent Engineering of Exosomes with Activatable Aptamer Probes for Specific Regulation and Monitoring of Cell Targeting.

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.