Target-Cell-Specific Bioorthogonal and Endogenous ATP Control of Signal Amplification for Intracellular MicroRNA Imaging

A stringent signal amplification method to profile microRNA (miRNA) expression within a specific cell remains a key challenge in biology. To address this issue, we report a target-cell-specific DNA nanosystem for endogenous adenosine-5′-triphosphate (ATP) bioorthogonal activation of the hybridizatio...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2021-01, Vol.93 (3), p.1693-1701
Main Authors: Meng, Xiangdan, Wang, Haijie, Yang, Meihuan, Li, Jing, Yang, Fan, Zhang, Kai, Dong, Haifeng, Zhang, Xueji
Format: Article
Language:English
Subjects:
Adenosine
Adenosine Triphosphate - metabolism
Amplification
Analytical chemistry
Aptamers
ATP
Biosensing Techniques
Cancer
Cell membranes
Chemistry
Deoxyribonucleic acid
DNA
Glutathione
Humans
Hybridization
MCF-7 Cells
Metal-organic frameworks
Metal-Organic Frameworks - chemistry
MicroRNAs
MicroRNAs - analysis
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Nucleic Acid Hybridization
Optical Imaging
Particle Size
Ribonucleic acid
RNA
Surface Properties
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Summary:A stringent signal amplification method to profile microRNA (miRNA) expression within a specific cell remains a key challenge in biology. To address this issue, we report a target-cell-specific DNA nanosystem for endogenous adenosine-5′-triphosphate (ATP) bioorthogonal activation of the hybridization chain reaction (HCR) to spatiotemporally controlled signal amplification detection of miRNA in vitro and in vivo. The system consists of ATP aptamer-sealed engineered HCR functional units combined with a cancer cell membrane-encapsulated glutathione (GSH)-responsive metal–organic framework (MOF). Once the nanosystem is specifically and efficiently internalized into a cancer cell through membrane-mediated homing targeting, the MOF structure degrades and releases HCR functional units. The endogenous high expressional ATP recognizes the aptamer, allowing the HCR functional units to adopt its active modality. The activated HCR functional units are then able to spatiotemporally and bioorthogonally image miRNA with high sensitivity in vitro and in vivo.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.0c04302