An Enzymatically Activated and Catalytic Hairpin Assembly-Driven Intelligent AND-Gated DNA Network for Tumor Molecular Imaging

Due to the potential off-tumor signal leakage and limited biomarker content, there is an urgent need for stimulus-responsive and amplification-based tumor molecular imaging strategies. Therefore, two tetrahedral framework DNA (tFNA-Hs), tFNA-H1AP, and tFNA-H2, were rationally engineered to form a po...

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Published in:Analytical chemistry (Washington) 2024-06, Vol.96 (24), p.10084-10091
Main Authors: Zhang, Mengxin, Zhang, Yingyu, Zhang, Xianwei, Liu, Kangbo, Li, Lifeng, Yu, Zhidan, Yuan, Jingya, Zhang, Wancun
Format: Article
Language:English
Subjects:
Animals
Apexes
Assembly
Biomarkers
Cell activation
Cytoplasm
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA - metabolism
DNA-(Apurinic or Apyrimidinic Site) Lyase - chemistry
DNA-(Apurinic or Apyrimidinic Site) Lyase - metabolism
Endonuclease
Humans
Hybridization
Imaging
MicroRNAs - analysis
MicroRNAs - metabolism
miRNA
Molecular Imaging - methods
Neuroblastoma
Optical Imaging
Tumors
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Summary:Due to the potential off-tumor signal leakage and limited biomarker content, there is an urgent need for stimulus-responsive and amplification-based tumor molecular imaging strategies. Therefore, two tetrahedral framework DNA (tFNA-Hs), tFNA-H1AP, and tFNA-H2, were rationally engineered to form a polymeric tFNA network, termed an intelligent DNA network, in an AND-gated manner. The intelligent DNA network was designed for tumor-specific molecular imaging by leveraging the elevated expression of apurinic/apyrimidinic endonuclease 1 (APE1) in tumor cytoplasm instead of normal cells and the high expression of miRNA-21 in tumor cytoplasm. The activation of tFNA-H1AP can be achieved through specific recognition and cleavage by APE1, targeting the apurinic/apyrimidinic site (AP site) modified within the stem region of hairpin 1 (H1AP). Subsequently, miRNA-21 facilitates the hybridization of activated H1AP on tFNA-H1AP with hairpin 2 (H2) on tFNA-H2, triggering a catalytic hairpin assembly (CHA) reaction that opens the H1AP at the vertices of tFNA-H1AP to bind with H2 at the vertices of tFNA-H2 and generate fluorescence signals. Upon completion of hybridization, miRNA-21 is released, initiating the subsequent cycle of the CHA reaction. The AND-gated intelligent DNA network can achieve specific tumor molecular imaging in vivo and also enables risk stratification of neuroblastoma patients.
ISSN:0003-2700
1520-6882
1520-6882
DOI:10.1021/acs.analchem.4c02076