Superparamagnetic iron oxide nanoparticles (SPION) with a "non-fouling" surface represent a versatile group of biocompatible nanomaterials valuable for medical diagnostics, including oncology. In our study we present a synthesis of novel maghemite (γ-Fe2O3) nanoparticles with positive and negative overall surface charge and their coating by copolymer P(HPMA-co-HAO) prepared by RAFT (reversible addition-fragmentation chain-transfer) copolymerization of N-(2-hydroxypropyl)methacrylamide (HPMA) with N-[2-(hydroxyamino)-2-oxo-ethyl]-2-methyl-prop-2-enamide (HAO). Coating was realized via hydroxamic acid groups of the HAO comonomer units with a strong affinity to maghemite. Dynamic light scattering (DLS) demonstrated high colloidal stability of the coated particles in a wide pH range, high ionic strength, and the presence of phosphate buffer (PBS) and serum albumin (BSE). Transmission electron microscopy (TEM) images show a narrow size distribution and spheroid shape. Alternative coatings were prepared by copolymerization of HPMA with methyl 2-(2-methylprop-2-enoylamino)acetate (MMA) and further post-polymerization modification with hydroxamic acid groups, carboxylic acid and primary-amino functionalities. Nevertheless, their colloidal stability was worse in comparison with P(HPMA-co-HAO). Additionally, P(HPMA-co-HAO)-coated nanoparticles were subjected to a bio-distribution study in mice. They were cleared from the blood stream by the liver relatively slowly, and their half-life in the liver depended on their charge; nevertheless, both cationic and anionic particles revealed a much shorter metabolic clearance rate than that of commercially available ferucarbotran.

• Keywords
• MRI, contrast agents, hydroxamic acid, maghemite, non-fouling surface, polymer coating, superparamagnetic iron oxide nanoparticles,
• Publication type
• Journal Article MeSH

Magnetic resonance imaging (MRI) of superparamagnetic iron oxide-labeled cells can be used as a non-invasive technique to track stem cells after transplantation. The aim of this study was to (1) evaluate labeling efficiency of D-mannose-coated maghemite nanoparticles (D-mannose(γ-Fe2O3)) in neural stem cells (NSCs) in comparison to the uncoated nanoparticles, (2) assess nanoparticle utilization as MRI contrast agent to visualize NSCs transplanted into the mouse brain, and (3) test nanoparticle biocompatibility. D-mannose(γ-Fe2O3) labeled the NSCs better than the uncoated nanoparticles. The labeled cells were visualized by ex vivo MRI and their localization subsequently confirmed on histological sections. Although the progenitor properties and differentiation of the NSCs were not affected by labeling, subtle effects on stem cells could be detected depending on dose increase, including changes in cell proliferation, viability, and neurosphere diameter. D-mannose coating of maghemite nanoparticles improved NSC labeling and allowed for NSC tracking by ex vivo MRI in the mouse brain, but further analysis of the eventual side effects might be necessary before translation to the clinic.

• Keywords
• brain, maghemite, magnetic resonance imaging, mouse, nanoparticles, neural stem cells,
• MeSH
• Cell Tracking methods   MeSH
• Magnetic Resonance Imaging methods   MeSH
• Magnetite Nanoparticles chemistry   MeSH
• Mannose chemistry   MeSH
• Brain cytology   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Neural Stem Cells cytology   transplantation   MeSH
• Ferric Compounds chemistry   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• ferric oxide MeSH Browser
• Magnetite Nanoparticles MeSH
• Mannose MeSH
• Ferric Compounds MeSH

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
• glycoconjugate, heparan sulfate proteoglycan, magnetic nanoparticles, poly-l-lysine, tea catechin,
• MeSH
• Cell Membrane metabolism   MeSH
• Dextrans chemistry   metabolism   MeSH
• Human Umbilical Vein Endothelial Cells MeSH
• Glioma drug therapy   pathology   MeSH
• HeLa Cells MeSH
• Heparan Sulfate Proteoglycans chemistry   metabolism   MeSH
• Humans MeSH
• Magnetite Nanoparticles administration & dosage   chemistry   MeSH
• Magnetic Fields MeSH
• Cell Line, Tumor MeSH
• Polylysine chemistry   metabolism   pharmacokinetics   MeSH
• Polysaccharide-Lyases metabolism   MeSH
• Microscopy, Electron, Transmission MeSH
• Iron metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Dextrans MeSH
• Heparan Sulfate Proteoglycans MeSH
• heparitinsulfate lyase MeSH Browser
• Magnetite Nanoparticles MeSH
• Polylysine MeSH
• Polysaccharide-Lyases MeSH
• Iron MeSH