PEGylated Nanoparticles Bind to and Alter Amyloid-Beta Peptide Conformation: Toward Engineering of Functional Nanomedicines for Alzheimer鈥檚 Disease
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- 作者：Davide Brambilla ; Romain Verpillot ; Benjamin Le Droumaguet ; Julien Nicolas ; Myriam Taverna ; Juraj K贸艌a ; Barbara Lettiero ; S. Hossein Hashemi ; Line De Kimpe ; Mara Canovi ; Marco Gobbi ; Val茅rie Nicolas ; Wiep Scheper ; S. Moein Moghimi ; Igor Tvaro拧ka ; Patrick Couvreur ; Karine Andrieux
- 刊名：ACS Nano
- 出版年：2012
- 出版时间：July 24, 2012
- 年：2012
- 卷：6
- 期：7
- 页码：5897-5908
- 全文大小：642K
- 年卷期：v.6,no.7(July 24, 2012)
- ISSN：1936-086X
文摘
We have demonstrated that the polyethylene glycol (PEG) corona of long-circulating polymeric nanoparticles (NPs) favors interaction with the amyloid-beta (A尾1鈥?2) peptide both in solution and in serum. The influence of PEGylation of poly(alkyl cyanoacrylate) and poly(lactic acid) NPs on the interaction with monomeric and soluble oligomeric forms of A尾1鈥?2 peptide was demonstrated by capillary electrophoresis, surface plasmon resonance, thioflavin T assay, and confocal microscopy, where the binding affected peptide aggregation kinetics. The capture of peptide by NPs in serum was also evidenced by fluorescence spectroscopy and ELISA. Moreover, in silico and modeling experiments highlighted the mode of PEG interaction with the A尾1鈥?2 peptide and its conformational changes at the nanoparticle surface. Finally, A尾1鈥?2 peptide binding to NPs affected neither complement activation in serum nor apolipoprotein-E (Apo-E) adsorption from the serum. These observations have crucial implications in NP safety and clearance kinetics from the blood. Apo-E deposition is of prime importance since it can also interact with the A尾1鈥?2 peptide and increase the affinity of NPs for the peptide in the blood. Collectively, our results suggest that these engineered long-circulating NPs may have the ability to capture the toxic forms of the A尾1鈥?2 peptide from the systemic circulation and potentially improve Alzheimer鈥檚 disease condition through the proposed 鈥?i>sink effect鈥?