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

Small. 2018 Jul;14(30):e1703115. doi: 10.1002/smll.201703115. Epub 2018 Jul 2.

Abstract

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

Keywords: brain; focused ultrasound; imaging; nanoclusters; positron emission tomography.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Blood-Brain Barrier / diagnostic imaging*
  • Blood-Brain Barrier / metabolism*
  • Gold / administration & dosage*
  • Metal Nanoparticles / administration & dosage*
  • Metal Nanoparticles / ultrastructure
  • Mice
  • Polyethylene Glycols / chemistry
  • Positron-Emission Tomography*
  • Surface Properties
  • Thioctic Acid / chemistry
  • Tissue Distribution
  • Ultrasonics / methods*

Substances

  • Polyethylene Glycols
  • Thioctic Acid
  • Gold