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

摘要

Focused ultrasound (FUS) technology is reported to enhance the delivery of ~(64)Cu-integrated ultrasmall gold nanoclusters (~(64)Cu-AuNCs) across the bloodbrain 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.