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Multiple Protective Roles of Nanoliposome-Incorporated Baicalein against Alpha-Synuclein Aggregates

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  • Farhang Aliakbari, National Institute for Genetic Engineering and Biotechnology Iran
  • ,
  • Hossein Mohammad-Beigi
  • ,
  • Shahsanam Abbasi, National Institute for Genetic Engineering and Biotechnology Iran
  • ,
  • Nasrollah Rezaei-Ghaleh, University of Göttingen
  • ,
  • Frederik Lermyte, University of Warwick
  • ,
  • Soha Parsafar, National Institute for Genetic Engineering and Biotechnology Iran
  • ,
  • Stefan Becker, Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute)
  • ,
  • Azita Parvaneh Tafreshi, National Institute for Genetic Engineering and Biotechnology Iran
  • ,
  • Peter B. O'Connor, University of Warwick
  • ,
  • Joanna F. Collingwood, University of Warwick
  • ,
  • Gunna Christiansen
  • ,
  • Duncan S. Sutherland
  • Poul Henning Jensen
  • Dina Morshedi, National Institute for Genetic Engineering and Biotechnology Iran
  • ,
  • Daniel E. Otzen

Nanoparticles are useful for increasing drug stability, solubility, and availability. The small molecule baicalein inhibits fibrillation, and detoxifies aggregates of α-synuclein (αSN) associated with Parkinson's disease (PD), but it suffers from instability, low solubility and consequent low availability. Here it is demonstrated that incorporation of baicalein into zwitterionic nanoliposomes (NLP-Ba) addresses these problems. NLP-Ba inhibits αSN fibril initiation, elongation, secondary nucleation, and also depolymerizes mature fibrils more effectively than free baicalein and prevents soluble αSN aggregates from seeding new fibrils. Importantly, NLP-Ba perturbs oligomers’ capacity to permeabilize the membrane. The interaction between NLP-Ba and αSN is confirmed by different biophysical techniques. This nanosystem crosses the blood-brain barrier in vitro and is effective against rotenone neurotoxicity in vivo. The effect of NLP-Ba on αSN fibrillation/cytotoxicity is attributed to a combination of free baicalein and empty NLPs. The results indicate a neuroprotective role for NLP-Ba in decreasing αSN pathogenicity in PD and highlight the use of nanoliposomes to mobilize poorly soluble hydrophobic drugs.

OriginalsprogEngelsk
Artikelnummer2007765
TidsskriftAdvanced Functional Materials
Vol/bind31
Nummer7
ISSN1616-301X
DOI
StatusUdgivet - 10 feb. 2021

Bibliografisk note

Funding Information:
This work was mainly supported by the Danish Research Council Medical Sciences, Denmark, to D.E.O. (Grant no. 4183‐00225), National Institute of Genetic Engineering and Biotechnology, Iran, to D.M. (Grant no. 990201‐I‐751 and T109), the Lundbeck Foundation, Denmark, to P.H.J. (Grant no. R180‐2014‐3545) and to D.E.O. (Grant no. R276‐2018‐671), and in part by the Engineering and Physical Sciences Research Council, UK, to J.F.C. (Grant no. EP/N033191/1), and a German Research Foundation (DFG) grant to N.R.‐G. (Grant no. RE3655/2‐1). The authors thank Markus Zweckstetter for generous access to NMR facilities. The authors thank Mohsen Farhadpour for designing the HPLC procedure to analyze dopamine content and Tayebeh Ghodselahi for providing gold nanoparticles. Karin Giller, Amir Tayaranian Marvian, Hamdam Hoorfar and Zahra Nayeri are acknowledged for preparation of NMR samples, graphical work, preparing the BBB model, network visualization and analysis, respectively.

Funding Information:
This work was mainly supported by the Danish Research Council Medical Sciences, Denmark, to D.E.O. (Grant no. 4183-00225), National Institute of Genetic Engineering and Biotechnology, Iran, to D.M. (Grant no. 990201-I-751 and T109), the Lundbeck Foundation, Denmark, to P.H.J. (Grant no. R180-2014-3545) and to D.E.O. (Grant no. R276-2018-671), and in part by the Engineering and Physical Sciences Research Council, UK, to J.F.C.?(Grant no. EP/N033191/1), and a German Research Foundation (DFG) grant to N.R.-G. (Grant no. RE3655/2-1). The authors thank Markus Zweckstetter for generous access to NMR facilities. The authors thank Mohsen Farhadpour for designing the HPLC procedure to analyze dopamine content and Tayebeh Ghodselahi for providing gold nanoparticles. Karin Giller, Amir Tayaranian Marvian, Hamdam Hoorfar and Zahra Nayeri are acknowledged for preparation of NMR samples, graphical work, preparing the BBB model, network visualization and analysis, respectively.

Publisher Copyright:
© 2020 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

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