Department of Mechanical Engineering and Material Science, Washington University in St. Louis, Saint Louis, MO 63130, USA.
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Control Release. 2018 Aug 10;283:143-150. doi: 10.1016/j.jconrel.2018.05.039. Epub 2018 Jun 1.
The goal of this study was to establish the feasibility of integrating focused ultrasound (FUS)-mediated delivery of Cu-integrated gold nanoclusters (Cu-AuNCs) to the pons for in vivo quantification of the nanocluster brain uptake using positron emission tomography (PET) imaging. FUS was targeted at the pons for the blood-brain barrier (BBB) disruption in the presence of systemically injected microbubbles, followed by the intravenous injection of Cu-AuNCs. The spatiotemporal distribution of the Cu-AuNCs in the brain was quantified using in vivo microPET/CT imaging at different time points post injection. Following PET imaging, the accumulation of radioactivity in the pons was further confirmed using autoradiography and gamma counting, and the gold concentration was quantified using inductively coupled plasma-mass spectrometry (ICP-MS). We found that the noninvasive and localized BBB opening by the FUS successfully delivered the Cu-AuNCs to the pons. We also demonstrated that in vivo real-time microPET/CT imaging was a reliable method for monitoring and quantifying the brain uptake of Cu-AuNCs delivered by the FUS. This drug delivery platform that integrates FUS, radiolabeled nanoclusters, and PET imaging provides a new strategy for noninvasive and localized nanoparticle delivery to the pons with concurrent in vivo quantitative imaging to evaluate delivery efficiency. The long-term goal is to apply this drug delivery platform to the treatment of pontine gliomas.
本研究的目的是确定将聚多巴胺包覆金纳米簇（Cu-AuNCs）通过聚焦超声（FUS）递送至脑桥用于使用正电子发射断层扫描（PET）成像进行体内纳米簇脑摄取的可行性。FUS 靶向脑桥，在全身注射微泡的情况下破坏血脑屏障（BBB），然后静脉注射 Cu-AuNCs。在注射后不同时间点使用体内 microPET/CT 成像定量测量脑内 Cu-AuNCs 的时空分布。进行 PET 成像后，使用放射自显影和伽马计数进一步确认放射性在脑桥的积聚，使用电感耦合等离子体质谱法（ICP-MS）定量测量金浓度。我们发现，FUS 的非侵入性和局部 BBB 开放成功地将 Cu-AuNCs 递送至脑桥。我们还证明，体内实时 microPET/CT 成像监测和定量测定 FUS 递送的 Cu-AuNCs 脑摄取的可靠方法。这种整合了 FUS、放射性标记纳米簇和 PET 成像的药物递送平台为非侵入性和局部递送至脑桥的纳米颗粒提供了一种新策略，同时进行体内定量成像以评估递药效率。长期目标是将这种药物递送平台应用于脑桥神经胶质瘤的治疗。
