Nanomedicine against Aβ aggregation by β–sheet breaker peptide delivery: In vitro evidence

Francesca Pederzoli, Barbara Ruozi, Jason Duskey, Simone Hagmeyer, Ann Katrin Sauer, Stefanie Grabrucker, Romina Coelho, Natalia Oddone, Ilaria Ottonelli, Eleonora Daini, Michele Zoli, Maria Angela Vandelli, Giovanni Tosi, Andreas M. Grabrucker

Research output: Contribution to journalArticlepeer-review

Abstract

The accumulation of amyloid β (Aβ) triggers a cascade of toxic events in Alzheimer’s disease (AD). The KLVFF peptide can interfere with Aβ aggregation. However, the peptide suffers from poor bioavailability and the inability to cross the blood–brain barrier. In this work, we study the possibility of adopting nanomedicine to overcome KLVFF limits in biodistribution. We produced new engineered polymeric nanoparticles (NPs), and we evaluated the cellular toxicity of these NPs and validated that KVLFF peptides released by NPs show the same promising effects on AD pathology. Our results revealed the successful generation of KVLFF loaded NPs that, without significant effects on cell heath, are even more potent in reversing Aβ-induced pathologies compared to the free peptide. Therefore, NPs will significantly advance KVLFF treatment as a therapeutic option for AD.

Original languageEnglish
Article number572
JournalPharmaceutics
Volume11
Issue number11
DOIs
Publication statusPublished - Nov 2019

Keywords

  • Alzheimer disease (AD)
  • Amyloid β
  • Blood-brain barrier (BBB)
  • KLVFF peptide
  • Polymeric nanoparticles (NPs)

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