Noninvasive and Spatiotemporal Control of DNAzyme-Based Imaging of Metal Ions In Vivo Using High-Intensity Focused Ultrasound

摘要

Detecting metal ionsin vivowith a high spatiotemporalresolution is critical to understanding the roles of the metal ions inboth healthy and disease states. Although spatiotemporal controls ofmetal-ion sensors using light have been demonstrated, the lack ofpenetration depth in tissue andin vivohas limited their application.To overcome this limitation, we herein report the use of high-intensity focused ultrasound (HIFU) to remotely deliver on-demand,spatiotemporally resolved thermal energy to activate the DNAzymesensors at the targeted region bothin vitroandin vivo.AZn2+-selective DNAzyme probe is inactivated by a protector strand to blockthe formation of catalytic enzyme structure, which can then beactivated by an HIFU-induced increase in the local temperature. Withthis design, Zn2+-specificfluorescent resonance energy transfer(FRET) imaging has been demonstrated by the new DNAzyme-HIFU probes in both HeLa cells and mice. The current method can be applied to monitor many other metal ions forin vivoimagingand medical diagnosis using metal-specific DNAzymes that have either been obtained or can be selected usingin vitroselection.