Glioblastoma Multiforme (GBM) is an aggressive brain cancer associated with high mortality. Current treatments including resection of 98% or more of the tumour result in median survival of less than 15 months. With such poor outcomes, innovative therapies are required. Ultrasmall Superparamagnetic Iron Oxide Nanoparticles (USPIONs) are emerging as potential treatments, however little is known on their effects on cells. Understanding interactions between USPIONs and GBM is critical in developing these therapies. The aim of this study is to investigate biological effects of USPION uptake on GBM cells in vitro.
CNS-1 cell cultures were exposed to 20µg/mL of USPIONs with a maghemite iron oxide cores, which mean core diameters are 10–15 nm. In order to measure the intake and the interaction of USPIONs on CNS-1, we have utilized different techniques including the transmission electron microscopy (TEM), iron quantification, mitochondrial membrane potential assay, Oxidative Stress Test, Mitochondrial Transition Pore Assay, flow cytometry, immunohistochemistry and western blotting.
Our results showed that USPIONs entered CNS-1 cells via clatherin coated pits which then became internalized in vacuoles. USPIONs induced Fenton Reaction, which potentially leads to the oxidative stress activating the Heat Shock Proteins (HSPs) protective mechanism. When this mechanism was overwhelmed, it led to a decrease in cell viability, however in due course, cells upregulated HSPs, re-activating these protective mechanisms which included the closure of mitochondrial permeability transition pore, limiting the release of pro-apoptotic cytochrome c, reducing oxidative stress and eventually recovering cell viability.
Ultrasmall superparamagnetic iron oxide nanoparticles interact with CNS-1, initiating the mitochondrial death pathway, however heat shock proteins are recruited, mitigating further apoptosis. Targeting CNS-1 protective mechanisms in conjunction with USPIONs exposure could induce a cytotoxic effect on CNS-1, providing insights for a novel therapy for this devastating disease.
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All authors have declared no conflicts of interest.