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

Focused ultrasound (FUS) technology is reported to enhance the delivery of 64Cu‐integrated ultrasmall gold nanoclusters (64Cu‐AuNCs) across the blood‐brain barrier (BBB) as measured by positron emission tomography (PET). To better define the optimal physical properties for brain delivery, 64Cu‐AuNCs...

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Bibliographic Details
Published in:Small (Weinheim an der Bergstrasse, Germany) Germany), 2018-07, Vol.14 (30), p.e1703115-n/a
Main Authors: Sultan, Deborah, Ye, Dezhuang, Heo, Gyu Seong, Zhang, Xiaohui, Luehmann, Hannah, Yue, Yimei, Detering, Lisa, Komarov, Sergey, Taylor, Sara, Tai, Yuan‐Chuan, Rubin, Joshua B., Chen, Hong, Liu, Yongjian
Format: Article
Language:English
Subjects:
Autoradiography
Brain
focused ultrasound
Gold
imaging
In vivo methods and tests
Medical imaging
Nanoclusters
Nanotechnology
Physical properties
Positron emission
positron emission tomography
Tomography
Ultrasonic imaging
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Summary:Focused ultrasound (FUS) technology is reported to enhance the delivery of 64Cu‐integrated ultrasmall gold nanoclusters (64Cu‐AuNCs) across the blood‐brain barrier (BBB) as measured by positron emission tomography (PET). To better define the optimal physical properties for brain delivery, 64Cu‐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 64Cu‐AuNCs. Quantitative PET imaging post‐FUS treatment shows site‐targeted brain penetration, retention, and diffusion of the negative, neutral, and positive 64Cu‐AuNCs. Autoradiography is performed to compare the intrabrain distribution of these nanoclusters. PET Imaging demonstrates the effective BBB opening and successful delivery of 64Cu‐AuNCs into the brain. Of the three 64Cu‐AuNCs investigated, the neutrally charged nanostructure performs the best and is the candidate platform for future theranostic applications in neuro‐oncology. A focused ultrasound and 64Cu integrated gold nanocluster (64Cu‐AuNCs) combined technology is developed to noninvasively image the trans‐blood brain barrier (BBB) delivery of 64Cu‐AuNCs through positron emission tomography in mice. The effects of nanocluster surface properties on the in vivo biodistribution, BBB penetration, retention, and diffusion are quantitatively determined. The intrabrain distribution profiles of various 64Cu‐AuNCs are also compared.
ISSN:1613-6810
1613-6829
DOI:10.1002/smll.201703115