Journal
NANOSCALE
Volume 9, Issue 42, Pages 16193-16199Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7nr05353c
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Funding
- Cancer Research UK Cambridge Centre Pump Prime Research Grant
- EPSRC-CRUK Cancer Imaging Centre in Cambridge and Manchester [C197/A16465]
- CRUK [C14303/A17197, C47594/A16267]
- EU-FP7-agreement [FP7-PEOPLE-2013-CIG-630729]
- ERASMUS
- UK EPSRC through NanoDTC [EP/G037221/1]
- EPSRC [EP/J017639/1]
- Herchel Smith postdoctoral fellowship
- ARAID foundation
- Cancer Research UK [21142, 16465, 16267] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/J017639/1] Funding Source: researchfish
- EPSRC [EP/J017639/1] Funding Source: UKRI
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Molecular rulers that rely on the Forster resonance energy transfer (FRET) mechanism are widely used to investigate dynamic molecular processes that occur on the nanometer scale. However, the capabilities of these fluorescence molecular rulers are fundamentally limited to shallow imaging depths by light scattering in biological samples. Photoacoustic tomography (PAT) has recently emerged as a high resolution modality for in vivo imaging, coupling optical excitation with ultrasound detection. In this paper, we report the capability of PAT to probe distance-dependent FRET at centimeter depths. Using DNA nanotechnology we created several nanostructures with precisely positioned fluorophore-quencher pairs over a range of nanoscale separation distances. PAT of the DNA nanostructures showed distance-dependent photoacoustic signal enhancement and demonstrated the ability of PAT to reveal the FRET process deep within tissue mimicking phantoms. Further, we experimentally validated these DNA nanostructures as a novel and biocompatible strategy to augment the intrinsic photoacoustic signal generation capabilities of small molecule fluorescent dyes.
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