Iron oxide nanoparticle enhancement of radiation cytotoxicity

Abstract

Iron oxide nanoparticles (IONPs) have been investigated as a promising means for inducing tumor cell-specific hyperthermia. Although the ability to generate and use nanoparticles that are biocompatible, tumor specific, and have the ability to produce adequate cytotoxic heat is very promising, significant preclinical and clinical development will be required for clinical efficacy. At this time it appears using IONP-induced hyperthermia as an adjunct to conventional cancer therapeutics, rather than as an independent treatment, will provide the initial IONP clinical treatment. Due to their high-Z characteristics, another option is to use intracellular IONPs to enhance radiation therapy without excitation with AMF (production of heat). To test this concept IONPs were added to cell culture media at a concentration of 0.2 mg Fe/mL and incubated with murine breast adenocarcinoma (MTG-B) cells for either 48 or 72 hours. Extracellular iron was then removed and all cells were irradiated at 4 Gy. Although samples incubated with IONPs for 48 hrs did not demonstrate enhanced post-irradiation cytotoxicity as compared to the non-IONP-containing cells, cells incubated with IONPs for 72 hours, which contained 40% more Fe than 48 hr incubated cells, showed a 25% decrease in clonogenic survival compared to their non-IONP-containing counterparts. These results suggest that a critical concentration of intracellular IONPs is necessary for enhancing radiation cytotoxicity.

Highly Porous Hybrid Metal–Organic Nanoparticles Loaded with Gemcitabine Monophosphate: a Multimodal Approach to Improve Chemo‐ and Radiotherapy

“…Remarkably, the equivalent iron concentration in the nanoMOFs used in this study was much lower than the one reported in previous studies with other iron oxide NPs (nanoMOFs contain 56 μM Fe compared to iron oxide NPs containing 3.6 mM ∼17.9 mM Fe). Moreover, the incubation time was also much shorter (6 h for nanoMOFs in comparison with 72 h for iron oxide NPs). The amount of Fe internalized in cells in the case of iron oxide NPs reached up to 40 pg/cell, whereas in this study, it was only 1.5 pg/cell.…”

“…This is comparable to the effects observed by Mazur et al . with iron oxide NPs, showing DEF (1‐4 Gy) values in the range of 1.1–1.6 . This clearly indicates that nanoMOFs enhance radiation effects.…”

Cytotoxic effects of crystalline silica in form of micro and nanoparticles on the human lung cell line A549

“…In this study, the effect of exposure time on the toxicity in the exposed cells was investigated, and the results indicated that by increasing exposure time, the rate of toxicity was higher because of the higher ROS generation, mitochondrial permeability, and decreased intracellular glutathione content. In other studies, exposure time also has been presented as an effective factor in cell uptake and increased toxicity (Pauluhn, 2012; Mazur et al, 2013). The failure of the cell cleansing mechanisms followed by increased exposure time could be a factor for a higher toxicity rate reported in some other studies (Bouallegui et al, 2018; Liu et al, 2020).…”

Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells

“…The follow-up studies also provided evidence for this promising application of IONs 126 - 128 . It was also reported that IONs were able to enhance radiation cytotoxicity of γ-rays 129 . In addition to IONs, other types of iron based-nanoparticles have shown radiosensitizing effects 130 .…”