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

Abstract

BackgroundPoly-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.MethodsPLL-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).ResultsCoadministration 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.ConclusionOur 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.

Scavenging of reactive oxygen species by phenolic compound-modified maghemite nanoparticles

“…However, the application of a magnetic field exerted either no increase or a minor increase in the MNP cell value of the phenolic compound-modified nanoparticles in L-929 or LN-229 cells, suggesting that phenolic modification may facilitate uptake to a level near the maximum uptake capacity. Our results were consistent with previous findings indicating that the application of a magnetic field did not facilitate cellular uptake of the magnetic nanoparticles [35–36].…”

<p>Effects of PEGylation on capture of dextran-coated magnetic nanoparticles in microcirculation</p>

“…Human umbilical vein endothelial cells (HUVECs) were obtained with a protocol approved by the institutional review board of Chang Gung Memorial Hospital to study MNP-HUVEC interaction, as described previously 38,40. HUVEC were cultured in M199 medium with FBS (10%), heparin (100 μg/mL), endothelial cell growth supplement (ECGS) (30 μg/mL) and penicillin/streptomycin/amphotericin (1%) at pH 7.4.…”

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

“…Compelling evidence has suggested that sulfonated and carboxylated groups from many proteoglycans are targeted by CNPs and are closely implicated in their endocytosis ( Figure 2 A). In fact, due to their high negative charge, heparin/heparan sulfate proteoglycans, and to a lower extent, chondroitin sulfate B proteoglycans were shown to be major contributors for CNP endocytosis [ 103 , 104 ]. These proteoglycans commonly referred to as syndecans, tend to cluster upon multivalent binding of CNPs and associate with actin-binding proteins or F-actin to initiate endocytosis, which can proceed through clathrin-dependent and -independent mechanisms [ 105 ].…”