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首页> 外文期刊>Biomaterials >Dual-functional nanoparticles targeting amyloid plaques in the brains of Alzheimer's disease mice
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Dual-functional nanoparticles targeting amyloid plaques in the brains of Alzheimer's disease mice

机译：针对阿尔茨海默氏病小鼠脑中淀粉样蛋白斑块的双功能纳米颗粒

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Alzheimer's disease (AD) is a common neurodegenerative disorder with few treatments. The limitations imposed by the blood-brain barrier (BBB) and the non-selective distribution of drugs in the brain have hindered the effective treatment of AD and may result in severe side effects on the normal brains. We developed a dual-functional nanoparticle drug delivery system based on a PEGylated poly (lactic acid) (PLA) polymer. Two targeting peptides that were screened by phage display, TGN and QSH, were conjugated to the surface of the nanoparticles. TGN specifically targets ligands at the BBB, while QSH has good affinity with Aβ1-42, which is the main component of amyloid plaque. Tests probing the bEnd.3 cell uptake and invivo imaging were conducted to determine the best density of TGN on the nanoparticles' surfaces. The optimal amount of QSH was studied using a Thioflavin T (ThT) binding assay and surface plasmon resonance (SPR) experiments. The optimal maleimide/peptide molar ratio was 3 for both TGN and QSH on the surface of the nanoparticles (T3Q3-NP), and these nanoparticles achieved enhanced and precise targeted delivery to amyloid plaque in the brains of AD model mice. A MTT assay also validated the safety of this dual-targeted delivery system; little cytotoxicity was demonstrated with both bEnd.3 and PC 12 cells. In conclusion, the T3Q3-NP might be a valuable targeting system for AD diagnosis and therapy.
机译：阿尔茨海默氏病（AD）是一种常见的神经退行性疾病，几乎没有治疗方法。血脑屏障（BBB）的局限性以及药物在大脑中的非选择性分布已经阻碍了AD的有效治疗，并可能导致对正常大脑的严重副作用。我们开发了基于PEG化聚（乳酸）（PLA）聚合物的双功能纳米颗粒药物递送系统。通过噬菌体展示筛选的两个靶向肽，TGN和QSH，被缀合到纳米颗粒的表面。 TGN专门针对BBB的配体，而QSH与Aβ1-42具有良好的亲和力，Aβ1-42是淀粉样斑块的主要成分。进行了探测bEnd.3细胞摄取和体内成像的测试，以确定纳米颗粒表面上TGN的最佳密度。使用硫黄素T（ThT）结合测定法和表面等离振子共振（SPR）实验研究了最佳QSH量。 TGN和QSH在纳米颗粒（T3Q3-NP）表面上的最佳马来酰亚胺/肽摩尔比均为3，并且这些纳米颗粒在AD模型小鼠的大脑中实现了增强且精确的靶向淀粉样斑块的靶向递送。 MTT分析也验证了这种双重目标递送系统的安全性。 bEnd.3和PC 12细胞均几乎没有细胞毒性。总之，T3Q3-NP可能是用于AD诊断和治疗的有价值的靶向系统。

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