Interaction of poly-L-lysine coating and heparan sulfate proteoglycan on magnetic nanoparticle uptake by tumor cells

Wei Xiong Siow,1,2 Yi-Ting Chang,1,2 Michal Babič,3 Yi-Ching Lu,2 Daniel Horák,3 Yunn-Hwa Ma1,2,4 1Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan, Republic of China; 2Department of Physiology and Pharmacology and Healthy Ag...

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Autores principales: Siow WX, Chang YT, Babič M, Lu YC, Horák D, Ma YH
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Publicado: Dove Medical Press 2018
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spelling oai:doaj.org-article:8508f8feab42445aa577e126aca157332021-12-02T05:28:43ZInteraction of poly-L-lysine coating and heparan sulfate proteoglycan on magnetic nanoparticle uptake by tumor cells1178-2013https://doaj.org/article/8508f8feab42445aa577e126aca157332018-03-01T00:00:00Zhttps://www.dovepress.com/interaction-of-poly-l-lysine-coating-and-heparan-sulfate-proteoglycan--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Wei Xiong Siow,1,2 Yi-Ting Chang,1,2 Michal Babič,3 Yi-Ching Lu,2 Daniel Horák,3 Yunn-Hwa Ma1,2,4 1Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan, Republic of China; 2Department of Physiology and Pharmacology and Healthy Aging Research Center, College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan, Republic of China; 3Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic; 4Department of Neurology, Chang Gung Memorial Hospital, Guishan, Taoyuan, Taiwan, Republic of China Background: Poly-L-lysine (PLL) enhances nanoparticle (NP) uptake, but the molecular mechanism remains unresolved. We asked whether PLL may interact with negatively charged glycoconjugates on the cell surface and facilitate uptake of magnetic NPs (MNPs) by tumor cells.Methods: PLL-coated MNPs (PLL-MNPs) with positive and negative ζ-potential were prepared and characterized. Confocal and transmission electron microscopy was used to analyze cellular internalization of MNPs. A colorimetric iron assay was used to quantitate cell-associated MNPs (MNPcell).Results: Coadministration of PLL and dextran-coated MNPs in culture enhanced cellular internalization of MNPs, with increased vesicle size and numbers/cell. MNPcell was increased by eight- to 12-fold in response to PLL in a concentration-dependent manner in human glioma and HeLa cells. However, the application of a magnetic field attenuated PLL-induced increase in MNPcell. PLL-coating increased MNPcell regardless of ζ-potential of PLL-MNPs, whereas magnetic force did not enhance MNPcell. In contrast, epigallocatechin gallate and magnetic force synergistically enhanced PLL-MNP uptake. In addition, heparin, but not sialic acid, greatly reduced the enhancement effects of PLL; however, removal of heparan sulfate from heparan sulfate proteoglycans of the cell surface by heparinase III significantly reduced MNPcell.Conclusion: Our results suggest that PLL-heparan sulfate proteoglycan interaction may be the first step mediating PLL-MNP internalization by tumor cells. Given these results, PLL may facilitate NP interaction with tumor cells via a molecular mechanism shared by infection machinery of certain viruses. Keywords: magnetic nanoparticles, poly-L-lysine, tea catechin, glycoconjugate, heparan sulfate proteoglycanSiow WXChang YTBabič MLu YCHorák DMa YHDove Medical Pressarticlemagnetic nanoparticlespoly-L-lysinetea catechinglycoconjugateheparan sulfate proteoglycanMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 1693-1706 (2018)
institution DOAJ
collection DOAJ
language EN
topic magnetic nanoparticles
poly-L-lysine
tea catechin
glycoconjugate
heparan sulfate proteoglycan
Medicine (General)
R5-920
spellingShingle magnetic nanoparticles
poly-L-lysine
tea catechin
glycoconjugate
heparan sulfate proteoglycan
Medicine (General)
R5-920
Siow WX
Chang YT
Babič M
Lu YC
Horák D
Ma YH
Interaction of poly-L-lysine coating and heparan sulfate proteoglycan on magnetic nanoparticle uptake by tumor cells
description Wei Xiong Siow,1,2 Yi-Ting Chang,1,2 Michal Babič,3 Yi-Ching Lu,2 Daniel Horák,3 Yunn-Hwa Ma1,2,4 1Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan, Republic of China; 2Department of Physiology and Pharmacology and Healthy Aging Research Center, College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan, Republic of China; 3Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague, Czech Republic; 4Department of Neurology, Chang Gung Memorial Hospital, Guishan, Taoyuan, Taiwan, Republic of China Background: Poly-L-lysine (PLL) enhances nanoparticle (NP) uptake, but the molecular mechanism remains unresolved. We asked whether PLL may interact with negatively charged glycoconjugates on the cell surface and facilitate uptake of magnetic NPs (MNPs) by tumor cells.Methods: PLL-coated MNPs (PLL-MNPs) with positive and negative ζ-potential were prepared and characterized. Confocal and transmission electron microscopy was used to analyze cellular internalization of MNPs. A colorimetric iron assay was used to quantitate cell-associated MNPs (MNPcell).Results: Coadministration of PLL and dextran-coated MNPs in culture enhanced cellular internalization of MNPs, with increased vesicle size and numbers/cell. MNPcell was increased by eight- to 12-fold in response to PLL in a concentration-dependent manner in human glioma and HeLa cells. However, the application of a magnetic field attenuated PLL-induced increase in MNPcell. PLL-coating increased MNPcell regardless of ζ-potential of PLL-MNPs, whereas magnetic force did not enhance MNPcell. In contrast, epigallocatechin gallate and magnetic force synergistically enhanced PLL-MNP uptake. In addition, heparin, but not sialic acid, greatly reduced the enhancement effects of PLL; however, removal of heparan sulfate from heparan sulfate proteoglycans of the cell surface by heparinase III significantly reduced MNPcell.Conclusion: Our results suggest that PLL-heparan sulfate proteoglycan interaction may be the first step mediating PLL-MNP internalization by tumor cells. Given these results, PLL may facilitate NP interaction with tumor cells via a molecular mechanism shared by infection machinery of certain viruses. Keywords: magnetic nanoparticles, poly-L-lysine, tea catechin, glycoconjugate, heparan sulfate proteoglycan
format article
author Siow WX
Chang YT
Babič M
Lu YC
Horák D
Ma YH
author_facet Siow WX
Chang YT
Babič M
Lu YC
Horák D
Ma YH
author_sort Siow WX
title Interaction of poly-L-lysine coating and heparan sulfate proteoglycan on magnetic nanoparticle uptake by tumor cells
title_short Interaction of poly-L-lysine coating and heparan sulfate proteoglycan on magnetic nanoparticle uptake by tumor cells
title_full Interaction of poly-L-lysine coating and heparan sulfate proteoglycan on magnetic nanoparticle uptake by tumor cells
title_fullStr Interaction of poly-L-lysine coating and heparan sulfate proteoglycan on magnetic nanoparticle uptake by tumor cells
title_full_unstemmed Interaction of poly-L-lysine coating and heparan sulfate proteoglycan on magnetic nanoparticle uptake by tumor cells
title_sort interaction of poly-l-lysine coating and heparan sulfate proteoglycan on magnetic nanoparticle uptake by tumor cells
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/8508f8feab42445aa577e126aca15733
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