An Enzyme‐Activatable Engineered DNAzyme Sensor for Cell‐Selective Imaging of Metal Ions

Abstract

There is intense interest in imaging intracellular metal ions because of their vital roles in many cellular processes. The challenge has been to develop chemical approaches that can detect metal ions in a cell‐type‐specific manner. Herein we report the design of an enzyme‐activatable DNAzyme sensor technology that can distinguish metal‐ion signals in tumor cells from those in normal cells both in vitro and in vivo. Specifically, the sensing activity of a traditional DNAzyme sensor was inhibited by engineering with a blocking sequence containing an abasic site that can be cleaved by cancer‐specific enzymes and thus enables the selective recovery of metal‐ion sensing capability in cancer cells. We demonstrated that the DNAzyme sensor not only enables cancer‐cell‐selective sensing and imaging of metal ions through an enzymically activated pathway, but also precise control over its metal‐ion sensing activity in tumor‐bearing mice. We envision the use of this biosensing technology to probe the biological roles of diverse metal ions in specific diseases.

“Repaired and Activated” DNAzyme Enables the Monitoring of DNA Alkylation Repair in Live Cells

“…[15] Owing to their unique sequence programmability and RNA-cleavage activity,DNAzymes have emerged as apowerful platform for biomolecular detection as well as gene regulation in vitro and in vivo. [16][17][18][19][20][21][22][23] Previous studies have suggested that DNAnucleotides in the catalytic core are conserved for DNAzymes to maintain their cleavage efficiency. [24] Based on this property,stimuli-responsive chemical modifications such as nitrobenzyl or phenylboronate have been exploited to regulate the activity of DNAzymes.…”

Bioorthogonal regulation of DNA circuits for smart intracellular microRNA imaging

“…[21][22][23] However, its application in living system is significantly constrained, due to the cumbersome chemical synthesis of photolabile groups on nucleobases, the limited penetration depth of light and the potential phototoxicity. As a result, the endogenous cue, such as small molecules, 24,25 RNAs, 26,27 or enzymes, 28,29 has supplement an alternative way to regulate the DNA circuits. For small molecules-activated strategy, e.g., ATP, 24 their corresponding aptamers are needed to inter-correlate with DNA circuits.…”

Heterostructures Made of Upconversion Nanoparticles and Metal–Organic Frameworks for Biomedical Applications

“…[ 18 , 19 , 20 ] Up to date, UCNPs have been processed by size regulation, host‐lattice modulation, core‐shell engineering, and surface ligands exchange and have been endowed with unique photochemical characteristics, [ 21 ] such as narrow emission bandwidth, resistance to photobleaching, long luminescence lifetime, and relatively higher photon energy. [ 22 ] Such fascinating characteristics make them promising materials to be used as biosensors, [ 23 , 24 ] imaging agents, [ 25 ] and therapeutics. [ 26 , 27 , 28 ] However,the applications of UCNPs in biomedical areas are still facing challenges due to the limited surface engineering strategies and low drug loading capacity.…”