Size Measurement of Extracellular Vesicles and Synthetic Liposomes: The Impact of the Hydration Shell and the Protein Corona

Zoltán Varga; Bence Fehér; Diána Kitka; András Wacha; Attila Bóta; Szilvia Berényi; Vitaliy Pipich; Jean Luc Fraikin

doi:10.1016/j.colsurfb.2020.111053

Size Measurement of Extracellular Vesicles and Synthetic Liposomes: The Impact of the Hydration Shell and the Protein Corona

Zoltán Varga, Bence Fehér, Diána Kitka, András Wacha, Attila Bóta, Szilvia Berényi, Vitaliy Pipich, Jean Luc Fraikin

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Abstract

Size characterization of extracellular vesicles (EVs) and drug delivery liposomes is of great importance in their applications in diagnosis and therapy of diseases. There are many different size characterization techniques used in the field, which often report different size values. Besides technological biases, these differences originate from the fact that various methods measure different physical quantities to determine particle size. In this study, the size of synthetic liposomes with nominal diameters of 50nm and 100nm, and red blood cell-derived EVs (REVs) were measured with established optical methods, such as dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA), and with emerging non-optical methods such as microfluidic resistive pulse sensing (MRPS) and very small-angle neutron scattering (VSANS). The comparison of the hydrodynamic sizes obtained by DLS and NTA with the sizes corresponding to the excluded volume of the particles by MRPS enabled the estimation of the thickness of the hydration shell of the particles. The comparison of diameter values corresponding to the boundary of the phospholipid bilayer obtained from VSANS measurements with MRPS size values revealed the thickness of the polyethylene glycol-layer in case of synthetic liposomes, and the thickness of the protein corona in case of REVs.

Original language	English (US)
Article number	111053
Journal	Colloids and Surfaces B: Biointerfaces
Volume	192
Early online date	Apr 19 2020
DOIs	https://doi.org/10.1016/j.colsurfb.2020.111053
State	Published - Aug 2020
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by the National Research, Development and Innovation Office NKFIH, Hungary under grant numbers PD 121326 and NVKP_16-1-2016-0007. ZV was supported by the J?nos Bolyai Research Fellowship. Part of this work is based upon experiments performed at the KWS-3 instrument operated by JCNS at the Heinz Maier-Leibnitz Zentrum (MLZ), Garching, Germany. ZV gratefully acknowledges the financial support provided by JCNS to perform the neutron scattering measurements at MLZ.

Funding Information:
This work was supported by the National Research, Development and Innovation Office NKFIH, Hungary under grant numbers PD 121326 and NVKP_16-1-2016-0007 . ZV was supported by the János Bolyai Research Fellowship . Part of this work is based upon experiments performed at the KWS-3 instrument operated by JCNS at the Heinz Maier-Leibnitz Zentrum (MLZ), Garching, Germany. ZV gratefully acknowledges the financial support provided by JCNS to perform the neutron scattering measurements at MLZ.

Publisher Copyright:
© 2020 The Author(s)

Keywords

exosome
liposomal drug delivery
microfluidic resistive pulse sensing
microparticle
small-angle neutron scattering

PubMed: MeSH publication types

Journal Article

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10.1016/j.colsurfb.2020.111053

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title = "Size Measurement of Extracellular Vesicles and Synthetic Liposomes: The Impact of the Hydration Shell and the Protein Corona",

abstract = "Size characterization of extracellular vesicles (EVs) and drug delivery liposomes is of great importance in their applications in diagnosis and therapy of diseases. There are many different size characterization techniques used in the field, which often report different size values. Besides technological biases, these differences originate from the fact that various methods measure different physical quantities to determine particle size. In this study, the size of synthetic liposomes with nominal diameters of 50nm and 100nm, and red blood cell-derived EVs (REVs) were measured with established optical methods, such as dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA), and with emerging non-optical methods such as microfluidic resistive pulse sensing (MRPS) and very small-angle neutron scattering (VSANS). The comparison of the hydrodynamic sizes obtained by DLS and NTA with the sizes corresponding to the excluded volume of the particles by MRPS enabled the estimation of the thickness of the hydration shell of the particles. The comparison of diameter values corresponding to the boundary of the phospholipid bilayer obtained from VSANS measurements with MRPS size values revealed the thickness of the polyethylene glycol-layer in case of synthetic liposomes, and the thickness of the protein corona in case of REVs.",

keywords = "exosome, liposomal drug delivery, microfluidic resistive pulse sensing, microparticle, small-angle neutron scattering",

author = "Zolt{\'a}n Varga and Bence Feh{\'e}r and Di{\'a}na Kitka and Andr{\'a}s Wacha and Attila B{\'o}ta and Szilvia Ber{\'e}nyi and Vitaliy Pipich and Fraikin, {Jean Luc}",

note = "Funding Information: This work was supported by the National Research, Development and Innovation Office NKFIH, Hungary under grant numbers PD 121326 and NVKP_16-1-2016-0007. ZV was supported by the J?nos Bolyai Research Fellowship. Part of this work is based upon experiments performed at the KWS-3 instrument operated by JCNS at the Heinz Maier-Leibnitz Zentrum (MLZ), Garching, Germany. ZV gratefully acknowledges the financial support provided by JCNS to perform the neutron scattering measurements at MLZ. Funding Information: This work was supported by the National Research, Development and Innovation Office NKFIH, Hungary under grant numbers PD 121326 and NVKP_16-1-2016-0007 . ZV was supported by the J{\'a}nos Bolyai Research Fellowship . Part of this work is based upon experiments performed at the KWS-3 instrument operated by JCNS at the Heinz Maier-Leibnitz Zentrum (MLZ), Garching, Germany. ZV gratefully acknowledges the financial support provided by JCNS to perform the neutron scattering measurements at MLZ. Publisher Copyright: {\textcopyright} 2020 The Author(s)",

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language = "English (US)",

volume = "192",

journal = "Colloids and Surfaces B: Biointerfaces",

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T1 - Size Measurement of Extracellular Vesicles and Synthetic Liposomes

T2 - The Impact of the Hydration Shell and the Protein Corona

AU - Varga, Zoltán

AU - Fehér, Bence

AU - Kitka, Diána

AU - Wacha, András

AU - Bóta, Attila

AU - Berényi, Szilvia

AU - Pipich, Vitaliy

AU - Fraikin, Jean Luc

N1 - Funding Information: This work was supported by the National Research, Development and Innovation Office NKFIH, Hungary under grant numbers PD 121326 and NVKP_16-1-2016-0007. ZV was supported by the J?nos Bolyai Research Fellowship. Part of this work is based upon experiments performed at the KWS-3 instrument operated by JCNS at the Heinz Maier-Leibnitz Zentrum (MLZ), Garching, Germany. ZV gratefully acknowledges the financial support provided by JCNS to perform the neutron scattering measurements at MLZ. Funding Information: This work was supported by the National Research, Development and Innovation Office NKFIH, Hungary under grant numbers PD 121326 and NVKP_16-1-2016-0007 . ZV was supported by the János Bolyai Research Fellowship . Part of this work is based upon experiments performed at the KWS-3 instrument operated by JCNS at the Heinz Maier-Leibnitz Zentrum (MLZ), Garching, Germany. ZV gratefully acknowledges the financial support provided by JCNS to perform the neutron scattering measurements at MLZ. Publisher Copyright: © 2020 The Author(s)

PY - 2020/8

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N2 - Size characterization of extracellular vesicles (EVs) and drug delivery liposomes is of great importance in their applications in diagnosis and therapy of diseases. There are many different size characterization techniques used in the field, which often report different size values. Besides technological biases, these differences originate from the fact that various methods measure different physical quantities to determine particle size. In this study, the size of synthetic liposomes with nominal diameters of 50nm and 100nm, and red blood cell-derived EVs (REVs) were measured with established optical methods, such as dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA), and with emerging non-optical methods such as microfluidic resistive pulse sensing (MRPS) and very small-angle neutron scattering (VSANS). The comparison of the hydrodynamic sizes obtained by DLS and NTA with the sizes corresponding to the excluded volume of the particles by MRPS enabled the estimation of the thickness of the hydration shell of the particles. The comparison of diameter values corresponding to the boundary of the phospholipid bilayer obtained from VSANS measurements with MRPS size values revealed the thickness of the polyethylene glycol-layer in case of synthetic liposomes, and the thickness of the protein corona in case of REVs.

AB - Size characterization of extracellular vesicles (EVs) and drug delivery liposomes is of great importance in their applications in diagnosis and therapy of diseases. There are many different size characterization techniques used in the field, which often report different size values. Besides technological biases, these differences originate from the fact that various methods measure different physical quantities to determine particle size. In this study, the size of synthetic liposomes with nominal diameters of 50nm and 100nm, and red blood cell-derived EVs (REVs) were measured with established optical methods, such as dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA), and with emerging non-optical methods such as microfluidic resistive pulse sensing (MRPS) and very small-angle neutron scattering (VSANS). The comparison of the hydrodynamic sizes obtained by DLS and NTA with the sizes corresponding to the excluded volume of the particles by MRPS enabled the estimation of the thickness of the hydration shell of the particles. The comparison of diameter values corresponding to the boundary of the phospholipid bilayer obtained from VSANS measurements with MRPS size values revealed the thickness of the polyethylene glycol-layer in case of synthetic liposomes, and the thickness of the protein corona in case of REVs.

KW - exosome

KW - liposomal drug delivery

KW - microfluidic resistive pulse sensing

KW - microparticle

KW - small-angle neutron scattering

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SN - 0927-7765

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JO - Colloids and Surfaces B: Biointerfaces

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ER -

Size Measurement of Extracellular Vesicles and Synthetic Liposomes: The Impact of the Hydration Shell and the Protein Corona

Abstract

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Keywords

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