Development of a smart nano-vehicle to target cerebrovascular amyloid deposits and brain parenchymal plaques observed in Alzheimer's disease and cerebral amyloid angiopathy.
Development of a smart nano-vehicle to target cerebrovascular amyloid deposits and brain parenchymal plaques observed in Alzheimer's disease and cerebral amyloid angiopathy.
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DOI：
10.1007/s11095-008-9688-y
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发表时间：
2008-11
影响因子：
3.7
通讯作者：
Kandimalla, Karunya K.
中科院分区：
文献类型：
--
作者：
Agyare, Edward K.;Curran, Geoffry L.;Ramakrishnan, Muthu;Yu, Caroline C.;Poduslo, Joseph F.;Kandimalla, Karunya K.
关键词：
设计一种能够穿透血脑屏障（BBB）的智能纳米载体（SNV），靶向阿尔茨海默病（AD）和脑血管淀粉样血管病（CAA）中形成的脑血管淀粉样蛋白。SNV由三聚磷酸盐离子凝胶法制备的壳聚糖聚合核组成。将抗淀粉样蛋白抗体IgG4.1的多胺修饰的F（ab’）部分包被在SNV表面作为生物传感器。一个类似的聚合核心包被牛血清白蛋白（BSA）作为对照纳米载体（CNV）。评价125I-SNVs和125I-CNVs在小鼠血脑屏障中的摄取情况。采用流式细胞术和共聚焦显微镜观察牛脑微血管内皮细胞（BBMECs）对SNVs和CNVs的摄取和胞吞作用。血浆清除率125I-SNVs比125I-CNVs高9倍。然而，125I-SNVs在大脑各区域的摄取比125I-CNVs高8 - 11倍。在BBMECs中，FITC-BSA负载snv的摄取是FITC-BSA负载cnv的两倍。共聚焦显微镜显示Alexa Fluor 647标记的snv，而不是cnv，在BBMEC单层中被摄取和胞吞。snv能够携带模型蛋白的有效载荷穿过血脑屏障以靶向脑淀粉样蛋白。
To design a smart nano-vehicle (SNV) capable of permeating the blood-brain barrier (BBB) to target cerebrovascular amyloid formed in both Alzheimer's disease (AD) and cerebrovascular amyloid angiopathy (CAA). SNV consists of a chitosan polymeric core prepared through ionic gelation with tripolyphosphate. A polyamine modified F(ab') portion of IgG4.1, an anti-amyloid antibody, was coated as a biosensor on the SNV surface. A similar polymeric core coated with bovine serum albumin (BSA) served as a control nano-vehicle (CNV). The BBB uptake of 125I-SNVs and 125I-CNVs was evaluated in mice. The uptake and transcytosis of SNVs and CNVs across bovine brain microvascular endothelial cells (BBMECs) was evaluated using flow cytometry and confocal microscopy. Plasma clearance of 125I-SNVs was nine times higher than that of the 125I-CNVs. However, the uptake of 125I-SNVs in various brain regions was about 8 to 11 times higher than that of 125I-CNVs. The uptake of FITC-BSA loaded SNVs in BBMECs was twice the uptake of FITC-BSA loaded CNVs. Confocal micrographs demonstrated the uptake and transcytosis of Alexa Fluor 647 labeled SNVs, but not CNVs, across the BBMEC monolayer. SNVs are capable of carrying a payload of model protein across the BBB to target cerebral amyloid.
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