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

Wei Xiong Siow, Yi Ting Chang, Michal Babič, Yi Ching Lu, Daniel Horák, Yunn Hwa Ma*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

32 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1693-1706
Number of pages14
JournalInternational Journal of Nanomedicine
Volume13
DOIs
StatePublished - 20 03 2018

Bibliographical note

Publisher Copyright:
© 2018 Siow et al. This work is published and licensed by Dove Medical Press Limited.

Keywords

  • Glycoconjugate
  • Heparan sulfate proteoglycan
  • Magnetic nanoparticles
  • Poly-l-lysine
  • Tea catechin

Fingerprint

Dive into the research topics of 'Interaction of poly-L-lysine coating and heparan sulfate proteoglycan on magnetic nanoparticle uptake by tumor cells'. Together they form a unique fingerprint.

Cite this