Abstract
While hyaluronic acid encapsulating superparamagnetic iron oxide nanoparticles have been reported to exhibit selective cytotoxicity toward cancer cells, it is unclear whether low-molecular-weight hyaluronic acid-conjugated superparamagnetic iron oxide nanoparticles also display such cytotoxicity. In this study, high-molecular-weight hyaluronic acid was irradiated with γ-ray, while Fe3O4 nanoparticles were fabricated using chemical co-precipitation. The low-molecular-weight hyaluronic acid and Fe3O4 nanoparticles were then combined according to a previous study. Size distribution, zeta potential, and the binding between hyaluronic acid and iron oxide nanoparticles were examined using dynamic light scattering and a nuclear magnetic resonance spectroscopy. The ability of the fabricated low-molecular-weight hyaluronic acid conjugated superparamagnetic iron oxide nanoparticles to target cancer cells was examined using time-of-flight secondary ion mass spectrometry and T2* weighted magnetic resonance images to compare iron signals in U87MG human glioblastoma and NIH3T3 normal fibroblast cell lines. Comparison showed that the present material could target U87MG cells at a higher rate than NIH3T3 control cells, with a viability inhibition rate of 34% observed at day two and no cytotoxicity observed in NIH3T3 normal fibroblasts during the three-day experimental period. Supported by mass spectrometry images confirming that the nanoparticles accumulated on the surface of cancer cells, the fabricated materials can reasonably be suggested as a candidate for both magnetic resonance imaging applications and as an injectable anticancer agent.
Highlights
Introduction iationsHyaluronic acid (HA) is a biopolymer based on natural polysaccharides
HA has been found to bind to the receptor of cluster of differentiation maker-44 (CD44), which is found in abundance on cancer cell membranes [4,5], and because tumor selectivity is an important issue for developing cancer treatment agents
Since particle sizes were under 30 nM, these prepared superparamagnetic iron oxide NPs (SPIONs) could pass through a superparamagnetic-ferromagnetic transition [30,31]
Summary
FeCl2 4H2 O andMaterial, Hyaluronic (molecular weightand kDa) were obtainedIndustry from. O, oleic acid and sodium nitrate were purchased from Nacalai Tesque (Kyoto, Japan). (MTT), 3-(4,5thylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and agarose were obtained. Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), andEagle agarose were obtained from. Eagle medium (DMEM), fetal bovine serum (FBS), and penicillin-streptomycin purchased from Gibco (Grand fetal bovine serum (FBS), and penicillin-streptomycin were purchased from. All other solvents and reagents were purchased from J.T. Baker (PhilIsland, NY, lipsburg, NJ,USA). USA).All other solvents and reagents were purchased from J.T. Baker (Phillipsburg, NJ, USA)
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