Programmable pH-responsive DNA Nanosensors for Imaging Exocytosis and Retrieval of Synaptic Vesicles

Exocytosis and retrieval of synaptic vesicles (SVs) are vital steps during neurotransmitter propagation between neurons. Visu-alization of this dynamics of SVs is significant for elucidating the mechanisms underlying synaptic transmission, but remains challenging without an efficient, reliable and biocompatible labelling method. In this work, we developed a pH-responsive rati-ometric DNA tetrahedral nanoprobes (pHadtnps) that could specifically label recycling SVs with high stability and effective background suppression. Based on the luminal pH alternation during the recycling of SVs, pHadtnps were able to illustrate their exocytosis and retrieval in real time. Moreover, with high programmability of DNA nanotechnology, these nanoprobes could be flexibly equipped with different functional moieties, holds great promise for developing various versatile tools for studying communication in neuronal networks.