期刊
BIOMATERIALS
卷 32, 期 23, 页码 5489-5497出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.04.020
关键词
Alzheimer disease (AD); amyloid beta (A beta); Antibody; Affinity; Liposomes; Surface plasmon resonance (SPR)
资金
- European Community [FP7/2007-2013, 212043]
Amyloid beta (A beta) aggregates are considered as possible targets for therapy and/or diagnosis of Alzheimer disease (AD), and nanoparticles functionalized with A beta-specific ligands are considered promising vehicles for imaging probes and therapeutic agents. Herein, we characterized the binding properties of nanoliposomes decorated with an anti-A beta monoclonal antibody (A beta-MAb). The A beta-MAb was obtained in mice by immunization with A beta antigen followed by hybridoma fusion. Surface Plasmon Resonance (SPR) studies confirmed the very high affinity of purified A beta-MAb for both A beta monomers and fibrils (K-D = 0.08 and 0.13 nM, respectively). The affinity of the biotinylated A beta-MAb, used thereafter for liposome decoration, was lower although still in the low nanomolar range (K-D = 2.1 and 1.6 nM,respectively). Biotin-streptavidin ligation method was used to decorate nanoliposomes with A beta-MAb, at different densities. IgG-decorated liposomes were generated by the same methodology, as control. Vesicles were monodisperse with mean diameters 124-134 nm and demonstrated good colloidal stability and integrity when incubated with serum proteins. When studied by SPR, A beta-MAb-liposomes, but not IgG-liposomes, markedly bound to A beta monomers and fibrils, immobilized on the chip. KD values (calculated on A beta-MAb content) were about 0.5 and 2 nm with liposomes at high and low A beta-MAb density, respectively. A beta-MAb-liposome binding to A beta fibrils was additionally confirmed by ultracentrifugation technique, in which interactions occur in solution under physiological conditions. Moreover, A beta-MAb-liposomes bound amyloid deposits in post-mortem AD brain samples, confirming the potential of these nanoparticles for the diagnosis and therapy of AD. (C) 2011 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据