Cancer Cytotoxicity of a Hybrid Hyaluronan-Superparamagnetic Iron Oxide Nanoparticle Material: An In-Vitro Evaluation

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.

Keywords

• hyaluronan
• superparamagnetic iron oxide nanoparticle
• cancer
• TOF-SIM