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Programmable Morphing DNA Nanodevice Enables Triple Signal Amplification for Long-Term Early Tumor Metastasis

Huajie Pang1,2, Run Yang1, Hexv Niu1

  • 1State Key Laboratory of Synthetic Biology, Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, Tianjin University, Tianjin, China.

Angewandte Chemie (International Ed. in English)
|April 29, 2026
PubMed
Summary

Researchers developed a programmable morphing DNA nanodevice (PMDN) for ultrasensitive detection of early tumor metastasis. This advanced imaging tool offers prolonged intracellular functionality and durable tumor localization, improving early cancer detection.

Keywords:
DNA structuresadaptive structural deformationfluorescent probessignal amplificationultrasensitive detection

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Area of Science:

  • Biomedical Engineering
  • Molecular Imaging
  • Nanotechnology

Background:

  • Early detection of tumor metastasis is crucial but challenging due to limitations in current imaging tools.
  • Existing methods often lack sensitivity and sustained intracellular functionality for tracking early metastatic signals.

Purpose of the Study:

  • To develop a novel DNA nanodevice for ultrasensitive and long-term detection of early metastatic biomarkers.
  • To engineer an environment-adaptive nanodevice capable of dual-stage intracellular assembly and signal amplification.

Main Methods:

  • A programmable morphing DNA nanodevice (PMDN) integrating catalytic hairpin assembly (CHA) with a hybrid network amplification mechanism was designed.
  • The PMDN undergoes conformational folding in lysosomes and secondary CHA cascade activation by cytoplasmic miR-221 for signal amplification.
  • In vivo and in vitro studies utilized MDA-MB-231 cells and a metastatic mouse model for evaluation.

Main Results:

  • PMDN demonstrated over a 200-fold improvement in detection sensitivity compared to conventional CHA systems.
  • The nanodevice exhibited persistent fluorescence in cells and durable tumor localization in vivo for over 10 days.
  • PMDN enabled early visualization of pulmonary micrometastases in a mouse model via miR-221-activated amplification.

Conclusions:

  • Programmable morphing DNA nanodevices offer a powerful platform for real-time monitoring of early metastasis.
  • This approach enables long-term molecular imaging in complex biological environments.
  • The developed nanodevice overcomes limitations of current tools for sensitive and sustained detection of metastatic signals.