Dynamically Long-Term Imaging of Cellular RNA by Fluorescent Carbon Dots with Surface Isoquinoline Moieties and Amines

Cellular RNA dynamics are closely associated with a vast range of physiological processes that are mostly long-lasting. To uncover the association between RNA dynamics and these processes, fluorescent RNA probes with high specificity, photostability, and biocompatibility are compulsory. Herein, a series of fluorescent carbon dots (CDs) have been prepared by one-pot hydrothermal treatment of o-, m-, or p-phenylenediamines with triethylenetetramine. Only CDs derived from the meta precursor (m-CDs) with excellent photostability and biocompatibility can specifically bind to cellular RNA, allowing successfully long-term (up to 3 days) monitoring of RNA dynamics during cell apoptosis, mitosis, and proliferation. This RNA affinity can be attributed to the isoquinoline moieties and amines on the surface of m-CDs, which can bind to RNA through pi-pi stacking and electrostatic bonding, respectively. The cellular internalization of m-CDs is time-, temperature-, ATP-, caveolar, and microtubule-dependent. Additionally, investigations on the in vivo behavior of m-CD suggest that they can be efficiently and rapidly excreted from the zebrafish larvae body after 48 h. Our results provide a powerful tool for clarifying complex relationships between RNA dynamics and basic biological processes, disease development, or drug interactions.