Robust DNA Cross-Linked Polymeric Lighting-Up Nanogel Facilitates Sensitive Live Cell MicroRNA Imaging

Accurate and specific imaging of low-abundance intracellular microRNAs (miRNAs) is crucial for monitoring cellular processes and disease diagnosis. Despite the fact that nucleic acid amplification technologies have shown great advantages for the detection of trace targets, their live cell imaging ap...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2022-11, Vol.94 (46), p.16079-16085
Main Authors: Yang, Fang, Li, Shunmei, Li, Xia, Yuan, Ruo, Xiang, Yun
Format: Article
Language:English
Subjects:
Amplification
Analytical chemistry
Biocompatibility
Biomedical materials
Biosensing Techniques - methods
Chemical synthesis
Chemistry
Confined spaces
Crosslinking
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA - genetics
DNA biosynthesis
DNA probes
Energy transfer
Fluorescence
Fluorescence resonance energy transfer
Hybridization
Kinetics
Lighting
Medical imaging
MicroRNAs
MicroRNAs - genetics
miRNA
Monitoring
Nanogels
Nuclease
Nucleic Acid Hybridization
Nucleic acids
Polymers
Probes
Reaction kinetics
Target detection
Toxicity
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Summary:Accurate and specific imaging of low-abundance intracellular microRNAs (miRNAs) is crucial for monitoring cellular processes and disease diagnosis. Despite the fact that nucleic acid amplification technologies have shown great advantages for the detection of trace targets, their live cell imaging applications remain a major challenge because of the insufficient stability and slow reaction kinetics of the probes in cellular delivery and imaging. Herein, we demonstrate the synthesis of DNA-cross-linked polymeric lighting-up nanogels (DPLNs) through the DNA hairpin-based hybridization chain reaction within nanoscale-confined space for monitoring and imaging live cell miRNA-21 with high sensitivity. Cascaded catalytic hairpin assembly of two hairpin signal probes confined in the DPLNs can be triggered by the target miRNA, causing substantially amplified fluorescence resonance energy transfer signals with accelerated reaction kinetics. Moreover, the DPLNs show low cytotoxicity and highly enhanced nuclease resistance and can be successfully delivered into live cells for imaging low levels of miRNA-21. In addition, the DPLN probes can be readily tuned by specific sequences for monitoring various molecular targets in live cells for important biological and biomedical applications.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.2c03217