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

Farhang Aliakbari; Hossein Mohammad-Beigi; Shahsanam Abbasi; Nasrollah Rezaei-Ghaleh; Frederik Lermyte; Soha Parsafar; Stefan Becker; Azita Parvaneh Tafreshi; Peter B. O'Connor; Joanna F. Collingwood; Gunna Christiansen; Duncan S. Sutherland; Poul Henning Jensen; Dina Morshedi; Daniel E. Otzen

doi:10.1002/adfm.202007765

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

Farhang Aliakbari, Hossein Mohammad-Beigi, Shahsanam Abbasi, Nasrollah Rezaei-Ghaleh, Frederik Lermyte, Soha Parsafar, Stefan Becker, Azita Parvaneh Tafreshi, Peter B. O'Connor, Joanna F. Collingwood, Gunna Christiansen, Duncan S. Sutherland, Poul Henning Jensen, Dina Morshedi, Daniel E. Otzen^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

16 Citations (Scopus)

Abstract

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.

Original language	English
Article number	2007765
Journal	Advanced Functional Materials
Volume	31
Issue number	7
ISSN	1616-301X
DOIs	https://doi.org/10.1002/adfm.202007765
Publication status	Published - 10 Feb 2021
Externally published	Yes

Keywords

baicalein
fibrillation
neurotoxicity
Parkinson's disease
zwitterionic nanoliposomes
α-synuclein

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Aliakbari, F., Mohammad-Beigi, H., Abbasi, S., Rezaei-Ghaleh, N., Lermyte, F., Parsafar, S., Becker, S., Tafreshi, A. P., O'Connor, P. B., Collingwood, J. F., Christiansen, G., Sutherland, D. S., Jensen, P. H., Morshedi, D., & Otzen, D. E. (2021). Multiple Protective Roles of Nanoliposome-Incorporated Baicalein against Alpha-Synuclein Aggregates. Advanced Functional Materials, 31(7), Article 2007765. https://doi.org/10.1002/adfm.202007765

@article{551f0528024d49b4a51767019d25912f,

title = "Multiple Protective Roles of Nanoliposome-Incorporated Baicalein against Alpha-Synuclein Aggregates",

abstract = "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{\textquoteright} 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.",

keywords = "baicalein, fibrillation, neurotoxicity, Parkinson's disease, zwitterionic nanoliposomes, α-synuclein",

author = "Farhang Aliakbari and Hossein Mohammad-Beigi and Shahsanam Abbasi and Nasrollah Rezaei-Ghaleh and Frederik Lermyte and Soha Parsafar and Stefan Becker and Tafreshi, {Azita Parvaneh} and O'Connor, {Peter B.} and Collingwood, {Joanna F.} and Gunna Christiansen and Sutherland, {Duncan S.} and Jensen, {Poul Henning} and Dina Morshedi and Otzen, {Daniel E.}",

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. Publisher Copyright: {\textcopyright} 2020 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2021",

month = feb,

day = "10",

doi = "10.1002/adfm.202007765",

language = "English",

volume = "31",

journal = "Advanced Functional Materials",

issn = "1616-301X",

publisher = "Wiley",

number = "7",

}

Aliakbari, F, Mohammad-Beigi, H, Abbasi, S, Rezaei-Ghaleh, N, Lermyte, F, Parsafar, S, Becker, S, Tafreshi, AP, O'Connor, PB, Collingwood, JF, Christiansen, G, Sutherland, DS, Jensen, PH, Morshedi, D & Otzen, DE 2021, 'Multiple Protective Roles of Nanoliposome-Incorporated Baicalein against Alpha-Synuclein Aggregates', Advanced Functional Materials, vol. 31, no. 7, 2007765. https://doi.org/10.1002/adfm.202007765

TY - JOUR

T1 - Multiple Protective Roles of Nanoliposome-Incorporated Baicalein against Alpha-Synuclein Aggregates

AU - Aliakbari, Farhang

AU - Mohammad-Beigi, Hossein

AU - Abbasi, Shahsanam

AU - Rezaei-Ghaleh, Nasrollah

AU - Lermyte, Frederik

AU - Parsafar, Soha

AU - Becker, Stefan

AU - Tafreshi, Azita Parvaneh

AU - O'Connor, Peter B.

AU - Collingwood, Joanna F.

AU - Christiansen, Gunna

AU - Sutherland, Duncan S.

AU - Jensen, Poul Henning

AU - Morshedi, Dina

AU - Otzen, Daniel E.

N1 - 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 2020 Elsevier B.V., All rights reserved.

PY - 2021/2/10

Y1 - 2021/2/10

N2 - 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.

AB - 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.

KW - baicalein

KW - fibrillation

KW - neurotoxicity

KW - Parkinson's disease

KW - zwitterionic nanoliposomes

KW - α-synuclein

UR - http://www.scopus.com/inward/record.url?scp=85096803173&partnerID=8YFLogxK

U2 - 10.1002/adfm.202007765

DO - 10.1002/adfm.202007765

M3 - Journal article

AN - SCOPUS:85096803173

SN - 1616-301X

VL - 31

JO - Advanced Functional Materials

JF - Advanced Functional Materials

IS - 7

M1 - 2007765

ER -

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

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