@article{b857cf7e9bba428aa365e2b2b5609a17,
title = "Focused Ultrasound Enabled Trans-Blood Brain Barrier Delivery of Gold Nanoclusters: Effect of Surface Charges and Quantification Using Positron Emission Tomography",
abstract = "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.",
keywords = "brain, focused ultrasound, imaging, nanoclusters, positron emission tomography",
author = "Deborah Sultan and Dezhuang Ye and Heo, {Gyu Seong} and Xiaohui Zhang and Hannah Luehmann and Yimei Yue and Lisa Detering and Sergey Komarov and Sara Taylor and Tai, {Yuan Chuan} and Rubin, {Joshua B.} and Hong Chen and Yongjian Liu",
note = "Funding Information: D.S. and D.Y. contributed equally to this work. Funding for this project (MC-II-2017-661) was provided by the Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital. This work was performed in part at the Nano Research Facility (NRF), a member of the National Nanotechnology Infrastructure Network (NNIN), which was supported by the National Science Foundation under Grant No. ECS-0335765. Any opinions, findings, conclusions, or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. NRF is part of the School of Engineering and Applied Science at Washington University in St. Louis. The authors thank Nicole Fettig, Margaret Morris, Amanda Klaas, and Lori Strong for their assistance with animals and imaging studies and Thomas Voller, Evelyn Madrid, and Paul Eisenbeis for 64Cu production. The ESI-MS results were acquired by use of the NIH/NIGMS Biomedical Mass Spectrometry Resource at Washington University in St. Louis, MO, which is supported by National Institutes of Health/National Institute of General Medical Sciences Grant (8P41GM103422). Experiments were performed in part through the use of Washington University Center for Cellular Imaging (WUCCI) supported by Washington University School of Medicine, The Children{\textquoteright}s Discovery Institute of Washington University, St. Louis Children{\textquoteright}s Hospital (CDI-CORE-2015-505), and the National Institute for Neurological Disorders and Stroke (NS086741). The authors acknowledge financial support from Washington University in St. Louis and the Institute of Materials Science and Engineering for the use of instruments and staff assistance. Funding Information: D.S. and D.Y. contributed equally to this work. Funding for this project (MC-II-2017-661) was provided by the Children's Discovery Institute of Washington University and St. Louis Children's Hospital. This work was performed in part at the Nano Research Facility (NRF), a member of the National Nanotechnology Infrastructure Network (NNIN), which was supported by the National Science Foundation under Grant No. ECS-0335765. Any opinions, findings, conclusions, or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. NRF is part of the School of Engineering and Applied Science at Washington University in St. Louis. The authors thank Nicole Fettig, Margaret Morris, Amanda Klaas, and Lori Strong for their assistance with animals and imaging studies and Thomas Voller, Evelyn Madrid, and Paul Eisenbeis for 64Cu production. The ESI-MS results were acquired by use of the NIH/NIGMS Biomedical Mass Spectrometry Resource at Washington University in St. Louis, MO, which is supported by National Institutes of Health/National Institute of General Medical Sciences Grant (8P41GM103422). Experiments were performed in part through the use of Washington University Center for Cellular Imaging (WUCCI) supported by Washington University School of Medicine, The Children's Discovery Institute of Washington University, St. Louis Children's Hospital (CDI-CORE-2015-505), and the National Institute for Neurological Disorders and Stroke (NS086741). The authors acknowledge financial support from Washington University in St. Louis and the Institute of Materials Science and Engineering for the use of instruments and staff assistance. Publisher Copyright: {\textcopyright} 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",
year = "2018",
month = jul,
day = "26",
doi = "10.1002/smll.201703115",
language = "English",
volume = "14",
journal = "Small",
issn = "1613-6810",
number = "30",
}