Construction of an endogenously activated catalytic DNA circuit for highly robust in vivo microRNA imaging

An Enzymatically Gated Catalytic Hairpin Assembly Delivered by Lipid Nanoparticles for the Tumor‐Specific Activation of Signal Amplification in miRNA Imaging

“…The enzyme‐activated probe (E‐CHA) was constructed by engineering CHA components with enzyme‐responsive units to allow for conditional signal amplification. Although enzyme‐triggered amplification strategy has been adopted for tumor cell‐specific RNA imaging, [23, 24] the approaches have not been proved to enable improved imaging performance in vivo in comparison to traditional methods (without enzyme triggering) after systemic administration of DNA probes. In this work, by the introduction of LNPs to combat biological barriers, we showed that L/E‐CHA allowed for tumor‐selective imaging of miRNA with enhanced signal contrast.…”

“…One strategy to solve the issue is to use exogenous light [18] or endogenous stimulus (e.g. pH, ATP, enzyme) [19][20][21][22][23][24] to regulate signal amplification (e.g. HCR and CHA) in a cancer cell-specific manner, thereby reducing imaging signals in normal cells.…”

An Enzymatically Gated Catalytic Hairpin Assembly Delivered by Lipid Nanoparticles for the Tumor‐Specific Activation of Signal Amplification in miRNA Imaging

“…The enzyme-activated probe (E-CHA) was constructed by engineering CHA components with enzyme-responsive units to allow for conditional signal amplification. Although enzyme-triggered amplification strategy has been adopted for tumor cell-specific RNA imaging, [23,24] the approaches have not been proved to enable improved imaging performance in vivo in comparison to traditional methods (without enzyme triggering) after systemic administration of DNA probes. In this work, by the introduction of LNPs to combat biological barriers, we showed that L/E-CHA allowed for tumor-selective imaging of miRNA with enhanced signal contrast.…”

“…In the design, human apurinic/apyrimidinic endonuclease 1 (APE1), an essential enzyme in base excision repair process, has been selected as the endogenous stimuli. Many studies reveal that APE1 is highly expressed in cytoplasm of cancer cells, but mainly exist in the nuclear region in normal cells, [39, 40] thus has been used for triggering biosensing specifically in cancer cells [23, 24, 41, 42] . The principle of E‐CHA has been depicted in Figure 1a.…”

“…Many studies reveal that APE1 is highly expressed in cytoplasm of cancer cells, but mainly exist in the nuclear region in normal cells, [39,40] thus has been used for triggering biosensing specifically in cancer cells. [23,24,41,42] The principle of E-CHA has been depicted in Figure 1a. In E-CHA system, the enzyme-responsive molecular beacon (EMB) was designed by introducing an abasic (AP) site (the red part), which was located at 8 th nucleotides from the 3'-end of EMB in the stem region.…”