Cellular uptake of PLGA nanoparticles targeted with anti-amyloid and anti-transferrin receptor antibodies for Alzheimer's disease treatment
Cellular uptake of PLGA nanoparticles targeted with anti-amyloid and anti-transferrin receptor antibodies for Alzheimer's disease treatment
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DOI：
10.1016/j.colsurfb.2016.04.041
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发表时间：
2016-09-01
影响因子：
5.8
通讯作者：
Pereira, Maria Carmo
中科院分区：
文献类型：
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作者：
Loureiro, Joana A.;Gomes, Barbara;Pereira, Maria Carmo
在过去的几十年中，据报道，设计用于药物通过血脑屏障（BBB）运输的纳米载体的相关工作已被报道。正在测试能够抑制与阿尔茨海默病 (AD) 相关的聚集体的新药物，例如肽 iA beta(5)，但最常见的缺点是由于血脑屏障渗透性表面积较低，无法以所需浓度到达大脑。我们的方法作为改善血脑屏障药物转运的概念验证，基于聚乳酸-乙醇酸共聚物 (PLGA) 纳米粒子，其表面用抗转铁蛋白受体单克隆抗体 (OX26) 和抗 A beta (DE2B4) 进行功能化，以将封装的 iA beta(5) 递送到大脑中。使用猪脑毛细血管内皮细胞（PBCEC）作为 BBB 模型来评估系统的功效和毒性。与没有单克隆抗体功能化的纳米颗粒（NP）相比，通过肽 iA beta（5）的受控递送的免疫纳米颗粒的摄取显着增加。 (C) 2016 Elsevier B.V. 保留所有权利。
During the last few decades, relevant efforts have been reported to design nanocarriers for drug transport through the blood brain barrier (BBB). New drugs, such as peptide iA beta(5), capable to inhibit the aggregates associated with Alzheimeris disease (AD) are being tested but the most frequent drawback is to reach the brain in the desired concentrations due to the low BBB permeability-surface area. Our approach, as a proof of concept to improve drug transport through the BBB, is based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles with surface functionalized with anti-transferrin receptor monoclonal antibody (OX26) and anti-A beta (DE2B4) to deliver encapsulated iA beta(5) into the brain. Porcine brain capillary endothelial cells (PBCECs) were used as a BBB model to evaluate the system efficacy and toxicity. The uptake of immune nanoparticles with a controlled delivery of the peptide iA beta(5) was substantially increased compared to the nanoparticles (NPs) without monoclonal antibody functionalization. (C) 2016 Elsevier B.V. All rights reserved.