Focused ultrasound-enabled delivery of radiolabeled nanoclusters to the pons.

Focused ultrasound-enabled delivery of radiolabeled nanoclusters to the pons.
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DOI:
10.1016/j.jconrel.2018.05.039
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发表时间:
2018-08-10
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Chen H
Chen H
中科院分区:
其他
文献类型:
--
作者:
Ye D;Sultan D;Zhang X;Yue Y;Heo GS;Kothapalli SVVN;Luehmann H;Tai YC;Rubin JB;Liu Y;Chen H

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本研究的目的是建立集成聚焦超声(FUS)介导的64铜集成金纳米团簇(64 Cu-AuNC)到脑桥的递送的可行性,用于使用正电子发射断层扫描(PET)成像的纳米团簇脑摄取的体内定量。在全身注射微泡的情况下,FUS靶向脑桥以破坏血脑屏障(BBB),然后静脉注射64 Cu-AuNC。在注射后的不同时间点,使用体内microPET/CT成像定量脑中64 Cu-AuNC的时空分布。PET成像后,使用放射自显影和γ计数进一步确认脑桥中放射性的累积,并使用电感耦合等离子体质谱法(ICP-MS)定量金浓度。我们发现,通过FUS的非侵入性和局部BBB开放可以成功地将64 Cu-AuNCs输送到脑桥。我们还证明,体内实时microPET/CT成像是监测和量化由FUS递送的64 Cu-AuNC的脑摄取的可靠方法。该药物递送平台整合了FUS、放射性标记的纳米簇和PET成像,为非侵入性和局部化的纳米颗粒递送到脑桥提供了一种新的策略,同时进行体内定量成像以评估递送效率。长期目标是将这种药物递送平台应用于脑桥胶质瘤的治疗。
The goal of this study was to establish the feasibility of integrating focused ultrasound (FUS)-mediated delivery of 64Cu-integrated gold nanoclusters (64Cu-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 64Cu-AuNCs. The spatiotemporal distribution of the 64Cu-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 can successfully deliver the 64Cu-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 64Cu-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.
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