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 af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

19 Citationer (Scopus)

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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.

Originalsprog	Engelsk
Artikelnummer	2007765
Tidsskrift	Advanced Functional Materials
Vol/bind	31
Nummer	7
ISSN	1616-301X
DOI	https://doi.org/10.1002/adfm.202007765
Status	Udgivet - 10 feb. 2021

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10.1002/adfm.202007765Licens: CC BY

Adv Funct Materials - 2020 - Aliakbari - Multiple Protective Roles of Nanoliposome‐Incorporated Baicalein againstForlagets udgivne version, 6,14 MBLicens: CC BY

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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), Artikel 2007765. https://doi.org/10.1002/adfm.202007765

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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.}",

year = "2021",

month = feb,

day = "10",

doi = "10.1002/adfm.202007765",

language = "English",

volume = "31",

journal = "Advanced Functional Materials",

issn = "1616-301X",

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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, bind 31, nr. 7, 2007765. https://doi.org/10.1002/adfm.202007765

Multiple Protective Roles of Nanoliposome-Incorporated Baicalein against Alpha-Synuclein Aggregates. / Aliakbari, Farhang; Mohammad-Beigi, Hossein; Abbasi, Shahsanam et al.
I: Advanced Functional Materials, Bind 31, Nr. 7, 2007765, 10.02.2021.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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.

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

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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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