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Researchers developed novel DNA-based molecular probes for deep-tissue imaging by creating a high-brightness NIR-II emitter and spectrum-matched quencher. This breakthrough enables enhanced molecular sensing and noninvasive monitoring in living subjects.

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Area of Science:

  • Biotechnology
  • Nanotechnology
  • Medical Imaging

Background:

  • DNA-based molecular probes are limited to the visible spectrum, hindering deep-tissue imaging due to poor light penetration.
  • Near-infrared II (NIR-II) fluorescence offers superior tissue penetration but lacks high-performance fluorophore-quencher pairs for probe development.

Purpose of the Study:

  • To overcome the limitations of visible-spectrum probes and develop robust DNA-based molecular probes operating in the NIR-II window.
  • To engineer a synergistic fluorophore-quencher combination for enhanced deep-tissue molecular sensing.

Main Methods:

  • Coengineered a high-brightness NIR-II emitter using a DNA strand, cyanine dye, and albumin scaffold.
  • Designed a spectrum-matched quencher via symmetry-breaking of the cognate chromophore for precise absorption-emission alignment.
  • Developed DNA-based NIR-II molecular probes (NMPs) using the DAC-783/Q783 combination.

Main Results:

  • Achieved a 10-fold higher NIR-II photoluminescence quantum yield compared to commercial dyes, enabling imaging beyond 8 mm tissue depth.
  • Demonstrated significantly higher quenching efficiency with the novel quencher compared to conventional ones.
  • Validated NMP-122 probe for noninvasive, real-time monitoring of drug-induced liver injury in mice, outperforming visible-window probes.

Conclusions:

  • Successfully extended the operational window of molecular probes into the NIR-II region.
  • Established a generalizable blueprint for designing custom fluorophore-quencher combinations for NIR-II applications.
  • Paved the way for clinical translation of NIR-II DNA nanotechnology for advanced molecular imaging.