Focused ultrasound combined with microbubble-mediated intranasal delivery of gold nanoclusters to the brain.
Focused ultrasound combined with microbubble-mediated intranasal delivery of gold nanoclusters to the brain.
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DOI：
10.1016/j.jconrel.2018.07.020
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发表时间：
2018-09-28
期刊：
影响因子：
--
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Ye D;Zhang X;Yue Y;Raliya R;Biswas P;Taylor S;Tai YC;Rubin JB;Liu Y;Chen H
聚焦超声联合微泡鼻内给药（FUSIN）是一种新的脑内给药技术。FUSIN利用鼻途径进行直接鼻-脑给药，从而绕过血脑屏障（BBB）并最大限度地减少全身暴露。它还使用FUS诱导的微泡空化来增强鼻内（IN）给药的药物向FUS靶向大脑位置的转运。先前的研究提供了概念验证数据，表明FUSIN将葡聚糖和脑源性神经营养因子递送到小鼠大脑尾壳核的可行性。本研究的目的是评估IN施用的金纳米簇（AuNC）的生物分布，并评估FUSIN用于将AuNC递送至脑干的可行性和短期安全性。进行了三个实验。首先，使用体内正电子发射断层扫描/计算机断层扫描（PET/CT）评估IN给药的64 Cu合金AuNC（64 Cu-AuNC）的全身生物分布，并使用离体γ计数进行验证。对照小鼠静脉内（IV）注射64 Cu-AuNC。第二，分别使用64 Cu-AuNC和德克萨斯红标记的AuNC（TR-AuNC）来评估脑中的FUSIN递送结果。通过鼻途径向小鼠施用64 Cu-AuNC或TR-AuNC，然后在全身注射的微泡存在下在脑干处进行FUS超声处理。分别通过离体脑片放射自显影和荧光显微镜检查64 Cu-AuNCs和TR-AuNCs的空间分布。第三，进行组织学分析以评价FUSIN处理后对鼻和脑的任何潜在组织学损伤。实验结果显示，与IV注射相比，IN施用诱导了显著更低的64 Cu-AuNC在血液、肺、肝、脾、肾和心脏中的积累。与单独IN递送相比，FUSIN增强了64 Cu-AuNC和TR-AuNC在FUS靶向脑区域的递送。在鼻、三叉神经和脑中未检测到组织学水平的组织损伤。这些结果表明，FUSIN是一种很有前途的技术，用于无创、空间靶向和安全地将纳米颗粒递送到大脑，全身暴露最小。
Focused ultrasound combined with microbubble-mediated intranasal delivery (FUSIN) is a new brain drug delivery technique. FUSIN utilizes the nasal route for direct nose-to-brain drug administration, thereby bypassing the blood-brain barrier (BBB) and minimizing systemic exposure. It also uses FUS-induced microbubble cavitation to enhance transport of intranasally (IN) administered agents to the FUS-targeted brain location. Previous studies have provided proof-of-concept data showing the feasibility of FUSIN to deliver dextran and the brain-derived neurotrophic factor to the caudate putamen of mouse brains. The objective of this study was to evaluate the biodistribution of IN administered gold nanoclusters (AuNCs) and assess the feasibility and short-term safety of FUSIN for the delivery of AuNCs to the brainstem. Three experiments were performed. First, the whole-body biodistribution of IN administered 64Cu-alloyed AuNCs (64Cu-AuNCs) was assessed using in vivo positron emission tomography/computed tomography (PET/CT) and verified with ex vivo gamma counting. Control mice were intravenously (IV) injected with the 64Cu-AuNCs. Second, 64Cu-AuNCs and Texas red-labeled AuNCs (TR-AuNCs) were used separately to evaluate FUSIN delivery outcome in the brain. 64Cu-AuNCs or TR-AuNCs were administered to mice through the nasal route, followed by FUS sonication at the brainstem in the presence of systemically injected microbubbles. The spatial distribution of 64Cu-AuNCs and TR-AuNCs were examined by autoradiography and fluorescence microscopy of ex vivo brain slices, respectively. Third, histological analysis was performed to evaluate any potential histological damage to the nose and brain after FUSIN treatment. The experimental results revealed that IN administration induced significantly lower 64Cu-AuNCs accumulation in the blood, lungs, liver, spleen, kidney, and heart compared with IV injection. FUSIN enhanced the delivery of 64Cu-AuNCs and TR-AuNCs at the FUS-targeted brain region compared with IN delivery alone. No histological-level tissue damage was detected in the nose, trigeminal nerve, and brain. These results suggest that FUSIN is a promising technique for noninvasive, spatially targeted, and safe delivery of nanoparticles to the brain with minimal systemic exposure.
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影响因子：
19.7
作者：
Hynynen, K;McDannold, N;Jolesz, FA
通讯作者：
Jolesz, FA
影响因子：
3.7
作者：
Benedict, C;Hallschmid, M;Kern, W
通讯作者：
Kern, W
DOI：
10.2217/17435889.3.5.703
发表时间：
2008-10
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Longmire M;Choyke PL;Kobayashi H
通讯作者：
Kobayashi H
影响因子：
6
作者：
Rashed HM;Shamma RN;Basalious EB
通讯作者：
Basalious EB
影响因子：
3.7
作者：
Chen H;Chen CC;Acosta C;Wu SY;Sun T;Konofagou EE
通讯作者：
Konofagou EE