کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9153 618 2010 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Lipid-based nanoparticles with high binding affinity for amyloid-β1–42 peptide
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
Lipid-based nanoparticles with high binding affinity for amyloid-β1–42 peptide
چکیده انگلیسی

The neurotoxic beta-amyloid peptide (Aβ), formed in anomalous amounts in Alzheimer’s disease (AD), is released as monomer and then undergoes aggregation forming oligomers, fibrils and plaques in diseased brains. Aβ aggregates are considered as possible targets for therapy and/or diagnosis of AD. Since nanoparticles (NPs) are promising vehicles for imaging probes and therapeutic agents, we realized and characterized two types of NPs (liposomes and solid lipid nanoparticles, 145 and 76 nm average size, respectively) functionalized to target Aβ1–42 with high affinity. Preliminary immunostaining studies identified anionic phospholipids [phosphatidic acid (PA) and cardiolipin (CL)] as suitable Aβ1–42 ligands. PA/CL-functionalized, but not plain, NPs interacted with Aβ1–42 aggregates as indicated by ultracentrifugation experiments, in which binding reaction occurred in solution, and by Surface Plasmon Resonance (SPR) experiments, in which NPs flowed onto immobilized Aβ1–42. All these experiments were carried out in buffered saline. SPR studies indicated that, when exposed on NPs surface, PA/CL display very high affinity for Aβ1–42 fibrils (22–60 nm), likely because of the occurrence of multivalent interactions which markedly decrease the dissociation of PA/CL NPs from Aβ. Noteworthy, PA/CL NPs did not bind to bovine serum albumin. The PA/CL NPs described in this work are endowed with the highest affinity for Aβ so far reported. These characteristics make our NPs a very promising vector for the targeted delivery of potential new diagnostic and therapeutic molecules to be tested in appropriate animal models.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 31, Issue 25, September 2010, Pages 6519–6529
نویسندگان
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