Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages

Shann S Yu1,2, Cheryl M Lau1, Susan N Thomas3, W Gray Jerome4, David J Maron5, James H Dickerson2,6, Jeffrey A Hubbell3, Todd D Giorgio1,2,7,81Department of Biomedical Engineering, Vanderbilt University, Nashville, 2Vanderbilt Institute of Nanoscale Science and Engineering, Nashville, TN, USA; 3Inst...

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Autores principales:	Dickerson JH, Maron DJ, Jerome WG, Thomas SN, Lau CM, Yu SS, Hubbell JA, Giorgio TD
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5e709290ed554cb2a70bd6e81d5032fb
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spelling	oai:doaj.org-article:5e709290ed554cb2a70bd6e81d5032fb2021-12-02T00:12:59ZSize- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages1176-91141178-2013https://doaj.org/article/5e709290ed554cb2a70bd6e81d5032fb2012-02-01T00:00:00Zhttp://www.dovepress.com/size--and-charge-dependent-non-specific-uptake-of-pegylated-nanopartic-a9272https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Shann S Yu1,2, Cheryl M Lau1, Susan N Thomas3, W Gray Jerome4, David J Maron5, James H Dickerson2,6, Jeffrey A Hubbell3, Todd D Giorgio1,2,7,81Department of Biomedical Engineering, Vanderbilt University, Nashville, 2Vanderbilt Institute of Nanoscale Science and Engineering, Nashville, TN, USA; 3Institute of Bioengineering, &Eacute;cole Polytechnique F&eacute;d&eacute;rale de Lausanne, Lausanne, Switzerland, 4Department of Pathology, Vanderbilt University Medical Center, Nashville, 5Vanderbilt Heart and Vascular Institute, Nashville, 6Department of Physics and Astronomy, Vanderbilt University, Nashville, 7Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, 8Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USAAbstract: The assessment of macrophage response to nanoparticles is a central component in the evaluation of new nanoparticle designs for future in vivo application. This work investigates which feature, nanoparticle size or charge, is more predictive of non-specific uptake of nanoparticles by macrophages. This was investigated by synthesizing a library of polymer-coated iron oxide micelles, spanning a range of 30&ndash;100 nm in diameter and -23 mV to +9 mV, and measuring internalization into macrophages in vitro. Nanoparticle size and charge both contributed towards non-specific uptake, but within the ranges investigated, size appears to be a more dominant predictor of uptake. Based on these results, a protease-responsive nanoparticle was synthesized, displaying a matrix metalloproteinase-9 (MMP-9)-cleavable polymeric corona. These nanoparticles are able to respond to MMP-9 activity through the shedding of 10&ndash;20 nm of hydrodynamic diameter. This MMP-9-triggered decrease in nanoparticle size also led to up to a six-fold decrease in nanoparticle internalization by macrophages and is observable by T2-weighted magnetic resonance imaging. These findings guide the design of imaging or therapeutic nanoparticles for in vivo targeting of macrophage activity in pathologic states.Keywords: macrophage targeting, poly(ethylene glycol) (PEG), poly(propylene sulfide) (PPS), iron oxides, opsonizationDickerson JHMaron DJJerome WGThomas SNLau CMYu SSHubbell JAGiorgio TDDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 799-813 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Dickerson JH Maron DJ Jerome WG Thomas SN Lau CM Yu SS Hubbell JA Giorgio TD Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages
description	Shann S Yu1,2, Cheryl M Lau1, Susan N Thomas3, W Gray Jerome4, David J Maron5, James H Dickerson2,6, Jeffrey A Hubbell3, Todd D Giorgio1,2,7,81Department of Biomedical Engineering, Vanderbilt University, Nashville, 2Vanderbilt Institute of Nanoscale Science and Engineering, Nashville, TN, USA; 3Institute of Bioengineering, &Eacute;cole Polytechnique F&eacute;d&eacute;rale de Lausanne, Lausanne, Switzerland, 4Department of Pathology, Vanderbilt University Medical Center, Nashville, 5Vanderbilt Heart and Vascular Institute, Nashville, 6Department of Physics and Astronomy, Vanderbilt University, Nashville, 7Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, 8Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USAAbstract: The assessment of macrophage response to nanoparticles is a central component in the evaluation of new nanoparticle designs for future in vivo application. This work investigates which feature, nanoparticle size or charge, is more predictive of non-specific uptake of nanoparticles by macrophages. This was investigated by synthesizing a library of polymer-coated iron oxide micelles, spanning a range of 30&ndash;100 nm in diameter and -23 mV to +9 mV, and measuring internalization into macrophages in vitro. Nanoparticle size and charge both contributed towards non-specific uptake, but within the ranges investigated, size appears to be a more dominant predictor of uptake. Based on these results, a protease-responsive nanoparticle was synthesized, displaying a matrix metalloproteinase-9 (MMP-9)-cleavable polymeric corona. These nanoparticles are able to respond to MMP-9 activity through the shedding of 10&ndash;20 nm of hydrodynamic diameter. This MMP-9-triggered decrease in nanoparticle size also led to up to a six-fold decrease in nanoparticle internalization by macrophages and is observable by T2-weighted magnetic resonance imaging. These findings guide the design of imaging or therapeutic nanoparticles for in vivo targeting of macrophage activity in pathologic states.Keywords: macrophage targeting, poly(ethylene glycol) (PEG), poly(propylene sulfide) (PPS), iron oxides, opsonization
format	article
author	Dickerson JH Maron DJ Jerome WG Thomas SN Lau CM Yu SS Hubbell JA Giorgio TD
author_facet	Dickerson JH Maron DJ Jerome WG Thomas SN Lau CM Yu SS Hubbell JA Giorgio TD
author_sort	Dickerson JH
title	Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages
title_short	Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages
title_full	Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages
title_fullStr	Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages
title_full_unstemmed	Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages
title_sort	size- and charge-dependent non-specific uptake of pegylated nanoparticles by macrophages
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/5e709290ed554cb2a70bd6e81d5032fb
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_version_	1718403869134815232

Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages

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