Combinatorial effects of radiofrequency hyperthermia and radiotherapy in the presence of magneto‐plasmonic nanoparticles on MCF‐7 breast cancer cells

Abstract

Here, the effects of combinatorial cancer therapy including radiotherapy (RT) and radiofrequency (RF) hyperthermia in the presence of gold-coated iron oxide nanoparticles (Au@IONPs), as a thermo-radio-sensitizer, are reported. The level of cell death and the ratio of Bax/Bcl2 genes, involved in the pathway of apoptosis, were measured to evaluate the synergistic effect of Au@IONPs-mediated RF hyperthermia and RT. MCF-7 human breast adenocarcinoma cells were treated with different concentrations of Au@IONPs. After incubation with NPs, the cells were exposed to RF waves (13.56 MHz; 100 W; 15 min). At the same time, thermometry was performed with an infrared (IR) camera. Then, the cells were exposed to 6 MV X-ray at various doses of 2 and 4 Gy. MTT (3-[4,5-dimethylthiazol-2-y1]-2, 5-diphenyltetrazolium bromide) assay was performed to evaluate cell viability and quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression ratio of Bax/Bcl2. Cellular uptake of nanoparticles was confirmed qualitatively and quantitatively. The results obtained from MTT assay and qRT-PCR studies showed that NPs and RF hyperthermia had no significant effect when applied separately, while their combination had synergistic effects on cell viability percentage and the level of apoptosis induction. A synergistic effect was also observed when the cancer cells were treated with a combination of NPs, RF hyperthermia, and RT. On the basis of the obtained results, it may be concluded that the use of magnetoplasmonic NPs in the process of hyperthermia and RT of cancer holds a great promise to develop a new combinatorial cancer therapy strategy. K E Y W O R D S cancer, combination therapy, magneto-plasmonic nanoparticles, radiofrequency hyperthermia, radiotherapy

Development of accurate temperature regulation culture system with metallic culture vessel demonstrates different thermal cytotoxicity in cancer and normal cells

“…6 , both BAX and BCL2 were strongly activated in cancer cells due to the thermal stimulus, while they were not in normal cells. Furthermore, the ratio of BAX / BCL2 , which is an index of apoptosis promotion, also differed dramatically between cancer and normal cells after thermal stimulation 15 .

Figure 6 Relative mRNA expression levels of apoptosis-related genes.

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“…It has been reported that HSP, which confers thermotolerance to cells, can also be expressed by mechanical stimulation rather than heat shock 25 . Alternatively, it was recently reported that combinations of hyperthermia and other stimuli enhanced the cell killing effect 10 , 15 , 26 , 27 . On the other hand, in previous studies, owing to the lack of a system that achieves immediate temperature regulation, there was a gap between the set temperature and the actual realized culture temperature to which cells were exposed.…”

“…The findings on the expression of genes involved in apoptosis also corresponded to the results of live cell numbers. Figure 6 indicates that the cancer cells were in the state of apoptosis, in contrast to the normal cells, because the ratio of BAX / BCL2 used as an index of apoptosis was dramatically changed in cancer cells due to the thermal stimulus 15 . As shown in Fig.…”

Focused ultrasound radiosensitizes human cancer cells by enhancement of DNA damage

“…Since HT-induced cytotoxicity and DNA damage can be observed during 24 h and these effects can be recovered by time as reported in the literature [41,42], it is essential to evaluate the cell metabolic activity with same time scale. In contrast, clonogenic assay, which is typically used in radiation research, measures the reproductive cell death by assessing the long-term effect after 2-3 weeks [43].…”

Transcriptional Regulation of the Colorectal Cancer Stem Cell Markers, Nanog and Oct4, Induced by a Thermodynamic-Based Therapy Approach

“…The previous study demonstrated that mild hypothermia or fever-range hyperthermia had inhibitory effect on viability/proliferation in glioblastoma, prostate, lung, breast cancer cell lines [16]. However, the other study has found that hyperthermia alone had no signi cant effect on breast cancer cells but its combination with radiotherapy has been useful for apoptosis [17]. Here, there is the gap in our knowledge and why we are doing this study on hyperthermia effects.…”