Programmable Morphing DNA Nanodevice Enables Triple Signal Amplification for Long‐Term Early Tumor Metastasis Imaging
Abstract
ABSTRACT Accurate early detection of tumor metastasis remains a formidable clinical challenge owing to the lack of imaging tools that can simultaneously respond sensitively to early metastatic signals and maintain enduring intracellular functionality. Here, we report a programmable morphing DNA nanodevice (PMDN) that integrates catalytic hairpin assembly (CHA) with a hybrid network amplification mechanism to achieve dual‐stage intracellular assembly and ultrasensitive detection of metastatic biomarkers. The acidic lysosomal milieu induces i‐motif‐mediated conformational folding into a compact and nuclease‐resistant structure. Following lysosomal escape, cytoplasmic miR‐221 triggers a secondary‐stage CHA cascade, driving large‐scale crosslinking of DNA monomers into a stable nanonetwork. This dynamic bottom‐up assembly ensures prolonged intracellular structural integrity of PMDN and concomitantly enables triple‐stage signal amplification. Compared with conventional CHA systems, PMDN achieves more than a 200‐fold improvement in detection sensitivity, exhibits remarkably persistent fluorescence in MDA‐MB‐231 cells, and maintains durable tumor localization in vivo for over 10 days. In a metastatic mouse model, PMDN enables early visualization of pulmonary micrometastases through miR‐221‐activated signal amplification. These results establish environment‐adaptive morphing DNA architectures as a powerful platform for real‐time monitoring of early metastasis and long‐term molecular imaging in complex biological environments.
Article Details
Authors (12)
Huajie Pang
State Key Laboratory of Synthetic Biology Tianjin Key Laboratory of Molecular Optoelectronic Sciences Department of Chemistry Tianjin University Tianjin China
Run Yang
Hexv Niu
State Key Laboratory of Synthetic Biology Tianjin Key Laboratory of Molecular Optoelectronic Sciences Department of Chemistry Tianjin University Tianjin China
Zhe Hao
Fanghua Zhang
State Key Laboratory of Synthetic Biology Tianjin Key Laboratory of Molecular Optoelectronic Sciences Department of Chemistry Tianjin University Tianjin China
Hongyan Zhang
Jinzheng Liu
State Key Laboratory of Synthetic Biology Tianjin Key Laboratory of Molecular Optoelectronic Sciences Department of Chemistry Tianjin University Tianjin China
Huiping Zang
State Key Laboratory of Synthetic Biology Tianjin Key Laboratory of Molecular Optoelectronic Sciences Department of Chemistry Tianjin University Tianjin China
Ruizhong Zhang
Xiaohong Wang
Department of Ophthalmology, Tianjin Medical University General Hospital, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Ocular Trauma, Laboratory of Molecular Ophthalmology, Tianjin Medical University
Xiyan Li
Institute of Photoelectronic Thin Film Devices and Technology, Tianjin Key Laboratory of Efficient Utilization of Solar Energy, Engineering Research Center of Thin Film Photoelectronic Technology of Ministry of Education, State Key Laboratory of Photovoltaic Materials and Cells
Libing Zhang
Beijing National Laboratory for Molecular Sciences, CAS Laboratory of Colloid and Interface and Thermodynamics, CAS Research/Education Center for Excellence in Molecular Sciences, Center for Carbon Neutral Chemistry