Focused Ultrasound Enabled Trans-Blood Brain Barrier Delivery of Gold Nanoclusters: Effect of Surface Charges and Quantification Using Positron Emission Tomography.
Authors: Sultan D, Ye D, Heo GS, Zhang X, Luehmann H, Yue Y, Detering L, Komarov S, Taylor S, Tai YC, Rubin JB, Chen H, Liu Y
Focused ultrasound (FUS) technology is reported to enhance the delivery of <sup>64</sup> Cu-integrated ultrasmall gold nanoclusters (<sup>64</sup> 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, <sup>64</sup> 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 <sup>64</sup> Cu-AuNCs. Quantitative PET imaging post-FUS treatment shows site-targeted brain penetration, retention, and diffusion of the negative, neutral, and positive <sup>64</sup> Cu-AuNCs. Autoradiography is performed to compare the intrabrain distribution of these nanoclusters. PET Imaging demonstrates the effective BBB opening and successful delivery of <sup>64</sup> Cu-AuNCs into the brain. Of the three <sup>64</sup> Cu-AuNCs investigated, the neutrally charged nanostructure performs the best and is the candidate platform for future theranostic applications in neuro-oncology.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To evaluate focused ultrasound–mediated trans-blood-brain barrier delivery of gold nanoclusters, investigate the effect of their surface charges on delivery, and quantify brain accumulation using positron emission tomography.
Animal model / Human subject
mouse, C57BL/6, 8 weeks, male
Disease model
healthy
Targeted brain region(s)
Striatum
Cargo name and characteristics
nanoparticle
Route of administration
intravenous
Outcomes and Safety
Summary of Outcomes
FUS-mediated BBB opening enabled the delivery of gold nanoclusters, with surface charge significantly influencing brain accumulation as quantified by PET.
Duration of biological effect
24 h
Safety-related matter
The procedure was reported as safe with no significant tissue damage at the applied 0.3 MPa pressure.
Brain Region
Ultrasound Parameters
Ultrasound instrument
single-element focused ultrasound transducer
FUS Frequency
1.0 MHz
FUS Intensity
0.3 MPa
FUS Pressure
not reported
FUS Mode
not reported
Pulse duration
10 ms
Duration of a single FUS session
60 s
We are open to feedback. If you see a mistake or have a suggestion, please contact us.
← Back to Search