Abstract
PurposeTo evaluate selective apoptosis of Y79 retinoblastoma versus ARPE-19 retinal pigment epithelial cells by using different doses of dextran-coated iron oxide nanoparticles (DCIONs) in a magnetic hyperthermia paradigm.MethodsY79 and ARPE-19 cells were exposed to different concentrations of DCIONs, namely, 0.25, 0.5, 0.75, and 1 mg/ml. After 2 hours of incubation, cells were exposed to a magnetic field with a frequency of 250 kHz and an amplitude of 4 kA/m for 30 minutes to raise the cellular temperature between 42 and 46°C. Y79 and ARPE-19 cells incubated with DCION without magnetic field exposure were used as controls. Cell viability and apoptosis were assessed at 4, 24, and 72 hours after hyperthermia treatment.ResultsAt 4 hours following magnetic hyperthermia, cell death for Y79 cells was 1%, 8%, 17%, and 17% for 0.25, 0.5, 0.75 and 1 mg/ml of DCION, respectively. Cell death increased to 47%, 59%, 70%, and 75% at 24 hours and 16%, 45%, 50%, and 56% at 72 hours for 0.25, 0.5, 0.75, and 1 mg/ml of DCIONs, respectively. Magnetic hyperthermia did not have any significant toxic effects on ARPE-19 cells at all DCION concentrations, and minimal baseline cytotoxicity of DCIONs on Y79 and ARPE-19 cells was observed without magnetic field activation. Gene expression profiling showed that genes involved in FAS and tumor necrosis factor alpha signaling pathways were activated in Y79 cells following hyperthermia. Caspase 3/7 activity in Y79 cells increased following treatment, consistent with the activation of caspase-mediated apoptosis and loss of cell viability by magnetic hyperthermia.ConclusionMagnetic hyperthermia using DCIONs selectively kills Y79 cells at 0.5 mg/ml or higher concentrations via the activation of apoptotic pathways.Translational RelevanceMagnetic hyperthermia using DCIONs might play a role in targeted management of retinoblastoma.
Highlights
Retinoblastoma is one of the most common malignant intraocular tumors in children
We evaluated the time course of cell death and the signaling pathways activated during magnetic hyperthermia of Y79 cells
We first tested the viability of Y79 retinoblastoma and ARPE-19 retinal pigment epithelium (RPE) cell lines by using different dextran-coated iron oxide nanoparticles (DCIONs) concentrations at 4, 24, and 72 hours following magnetic hyperthermia treatment (Fig. 1)
Summary
Retinoblastoma is one of the most common malignant intraocular tumors in children. In the United States, it is estimated that about 12 children per million under the age of 5 years are affected by this cancer.[1] In recent years, significant progress has been made in the treatment of retinoblastoma with the introduction of intra-arterial and intravitreal chemotherapy, and as a result, the survival rate reached above 90% in developed countries.[2,3] A recent literature review showed that the globe salvage rate is 90% to 100% for groups A to C eyes, more than 70% for group D eyes, and 51% for group E eyes following the intra-arterial chemotherapy. The primary reason for treatment failure in groups D and E was the presence of intravitreous seeds. Intra-arterial chemotherapy requires an experienced team and advanced equipment, which are limited to few centers.[4,5] With the recent development of safe injection techniques, TVST j 2019 j Vol 8 j No 5 j Article 18
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