Impact of superparamagnetic iron oxide nanoparticles on in vitro and in vivo radiosensitisation of cancer cells

Abstract

Purpose The recent implementation of MR-Linacs has highlighted theranostic opportunities of contrast agents in both imaging and radiotherapy. There is a lack of data exploring the potential of superparamagnetic iron oxide nanoparticles (SPIONs) as radiosensitisers. Through preclinical 225 kVp exposures, this study aimed to characterise the uptake and radiobiological effects of SPIONs in tumour cell models in vitro and to provide proof-of-principle application in a xenograft tumour model. Methods SPIONs were also characterised to determine their hydrodynamic radius using dynamic light scattering and uptake was measured using ICP-MS in 6 cancer cell lines; H460, MiaPaCa2, DU145, MCF7, U87 and HEPG2. The impact of SPIONs on radiobiological response was determined by measuring DNA damage using 53BP1 immunofluorescence and cell survival. Sensitisation Enhancement Ratios (SERs) were compared with the predicted Dose Enhancement Ratios (DEFs) based on physical absorption estimations. In vivo efficacy was demonstrated using a subcutaneous H460 xenograft tumour model in SCID mice by following intra-tumoural injection of SPIONs. Results The hydrodynamic radius was found to be between 110 and 130 nm, with evidence of being monodisperse in nature. SPIONs significantly increased DNA damage in all cell lines with the exception of U87 cells at a dose of 1 Gy, 1 h post-irradiation. Levels of DNA damage correlated with the cell survival, in which all cell lines except U87 cells showed an increased sensitivity (P < 0.05) in the linear quadratic curve fit for 1 h exposure to 23.5 μg/ml SPIONs. There was also a 30.1% increase in the number of DNA damage foci found for HEPG2 cells at 2 Gy. No strong correlation was found between SPION uptake and DNA damage at any dose, yet the biological consequences of SPIONs on radiosensitisation were found to be much greater, with SERs up to 1.28 ± 0.03, compared with predicted physical dose enhancement levels of 1.0001. In vivo, intra-tumoural injection of SPIONs combined with radiation showed significant tumour growth delay compared to animals treated with radiation or SPIONs alone (P < 0.05). Conclusions SPIONs showed radiosensitising effects in 5 out of 6 cancer cell lines. No correlation was found between the cell-specific uptake of SPIONs into the cells and DNA damage levels. The in vivo study found a significant decrease in the tumour growth rate.

Magnetic Nanoparticles Used in Oncology

“…Tumor radiosensitization is an important phenomenon, and it can be enhanced by combining classical radiotherapy with different drugs or even with magnetic nanoparticles. Magnetic nanoparticles present a high value of the atomic number Z and exhibit important X-ray photon absorption, leading to an increase in secondary electrons that produce human DNA deterioration when the radiation dose is increased [141]. Nanoparticles, which are characterized by a high proton number, are usually linked to increased oxidative stress, expressed by reactive oxygen species (ROS) such as hydroxyl radicals that damages the cells' DNA.…”

Improve the cytotoxic effects of megavoltage radiation treatment by Fe3O4@Cus–PEG nanoparticles as a novel radiosensitizer in colorectal cancer cells

“…Consequently, it would be significantly important to develop new approaches to enhance the treatment efficacy. One of the most effective methods is the combination of radiation therapy with radiosensitizer agents (Huynh et al 2021;Russell et al 2021).…”

“…In the meanwhile, many different types of metal nanoparticles have been reported as radiosensitizers, such as gold (Huynh et al 2021;Penninckx et al 2020), hafnium oxide (Chen et al 2016;Maggiorella et al 2012), copper (Jiang et al 2018;Liu et al 2017), bismuth (Guo et al 2017;Wang et al 2016), gadolinium (Delorme et al 2017;Mi et al 2015), and iron oxide-based nanoparticles (Nosrati et al 2021;Russell et al 2021).…”

“…However, it is expensive and more doses of gold nanoparticles are required to achieve significant dose enhancement. To overcome this limitation, we focused on copper and iron oxide nanoparticles for these reasons: they are much cheaper than gold nanoparticles (Huang et al 2020), can be used in photothermal therapy, and serve as radiosensitizer agents (Hadi et al 2020;Huang et al 2019;Russell et al 2021;Rybka 2019).…”

Gafchromic™ EBT3 Film Measurements of Dose Enhancement Effects by Metallic Nanoparticles for 192Ir Brachytherapy, Proton, Photon and Electron Radiotherapy

“…Compared with AuNPs and BiONPs, iron oxide NPs have a lower X-ray absorption coefficient due to their lower Z number (Fe; Z = 26), yet are still practical for DE applications [35,36]. When radiation was combined with superparamagnetic iron oxide NPs (SPIONs) in mice, radiosensitization was verified, as tumor growth rate was significantly decreased [37]. The SPIONs could also double as dose enhancers and contrast agents for magnetic resonance imaging (MRI).…”