PEGylated nanoparticles bind to and alter amyloid-beta peptide conformation: Toward engineering of functional nanomedicines for alzheimer's disease

Davide Brambilla, Romain Verpillot, Benjamin Le Droumaguet, Julien Nicolas, Myriam Taverna, Juraj Kóňa, Barbara Lettiero, S. Hossein Hashemi, Line De Kimpe, Mara Canovi, Marco Gobbi, Valérie Nicolas, Wiep Scheper, S. Moein Moghimi, Igor Tvaroška, Patrick Couvreur, Karine Andrieux

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

Abstract

We have demonstrated that the polyethylene glycol (PEG) corona of long-circulating polymeric nanoparticles (NPs) favors interaction with the amyloid-beta (Aβ 1-42) 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 Aβ 1-42 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 Aβ 1-42 peptide and its conformational changes at the nanoparticle surface. Finally, Aβ 1-42 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 Aβ 1-42 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 Aβ 1-42 peptide from the systemic circulation and potentially improve Alzheimer's disease condition through the proposed "sink effect".

Original languageEnglish (US)
Pages (from-to)5897-5908
Number of pages12
JournalACS Nano
Volume6
Issue number7
DOIs
StatePublished - Jul 24 2012

Keywords

  • Alzheimer's disease
  • binding
  • nanoparticles
  • polyethylene glycol

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

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