4.8 Article

Focused Ultrasound Enabled Trans-Blood Brain Barrier Delivery of Gold Nanoclusters: Effect of Surface Charges and Quantification Using Positron Emission Tomography

Journal

SMALL
Volume 14, Issue 30, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.201703115

Keywords

brain; focused ultrasound; imaging; nanoclusters; positron emission tomography

Funding

  1. Children's Discovery Institute of Washington University [MC-II-2017-661]
  2. National Science Foundation [ECS-0335765]
  3. National Institutes of Health/National Institute of General Medical Sciences [8P41GM103422]
  4. The Children's Discovery Institute of Washington University, St. Louis Children's Hospital [CDI-CORE-2015-505]
  5. National Institute for Neurological Disorders and Stroke [N5086741]
  6. Washington University in St. Louis
  7. Institute of Materials Science and Engineering
  8. St. Louis Children's Hospital [MC-II-2017-661]
  9. Washington University School of Medicine

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Focused ultrasound (FUS) technology is reported to enhance the delivery of Cu-64-integrated ultrasmall gold nanoclusters (Cu-64-AuNCs) across the blood-brain barrier (BBB) as measured by positron emission tomography (PET). To better define the optimal physical properties for brain delivery, Cu-64-AuNCs with different surface charges are synthesized and characterized. In vivo biodistribution studies are performed to compare the individual organ uptake of each type of Cu-64-AuNCs. Quantitative PET imaging post-FUS treatment shows site-targeted brain penetration, retention, and diffusion of the negative, neutral, and positive Cu-64-AuNCs. Autoradiography is performed to compare the intrabrain distribution of these nanoclusters. PET Imaging demonstrates the effective BBB opening and successful delivery of Cu-64-AuNCs into the brain. Of the three Cu-64-AuNCs investigated, the neutrally charged nanostructure performs the best and is the candidate platform for future theranostic applications in neuro-oncology.

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