A Pilot Study Into the Use of FDG-mNP as an Alternative Approach in Neuroblastoma Cell Hyperthermia

Abstract

Purpose Herein, we present a pilot study concerning the use of fluorodeoxy glucose conjugated magnetite nanoparticles as a potential agent in magnetic nanoparticle mediated neuroblastoma cancer cell hyperthermia. This approach makes use of the ‘Warburg effect’, utilising the fact that cancer cells have a higher metabolic rate than normal cells. Materials and methods FDG-mNP were synthesized, then applied to the SH-SY5Y neuroblastoma cancer cell line and exposed to an AC magnetic field. 3D Calorimetry was performed on the FDG-mNP compound. Simulations were performed using SEMCAD X software using Thelonious, (an anatomically correct male child model) in order to understand more about the end requirements with respect to cancer cell destruction. Results We investigated FDG-mNP mediated neuroblastoma cytotoxicity in conjunction with AC magnetic field exposure. Results are presented for 3D FDG-mNP SARmnp (10.86 ± 0.99 W/g of particles) using a therapeutic dose of 0.83 mg/mL. Human model simulations suggest that 43 W/kg SARTheo would be required to obtain 42 °C within the centre of a liver tumour (Tumour size, bounding box x=64, y=61, z=65 [mm]), and that the temperature distribution is inhomogeneous within the tumour. Conclusion Our study suggests that this approach could potentially be used to increase the temperature within cells that would result in cancer cell death due to hyperthermia. Further development of this research will also involve using whole tumours removed from living organisms in conjunction with magnetic resonance imaging and positron emission tomography.

Tissue Morphology and Gene Expression Characterisation of Transplantable Adenocarcinoma Bearing Mice Exposed to Fluorodeoxyglucose-Conjugated Magnetic Nanoparticles

“…We have demonstrated previously that FDG-MNPs are actively taken up within MCF-7 cancer cells in vitro. 25 Following magnetic field stimulation, we observed that FDG-MNPs led to rapid and sustained cellular hyperthermia, inducing a cell death rate of 89%. However, we also observed a cell death rate of 72% when exposed to the FDG-MNPs when not placed within a magnetic field, suggestive of potential toxicity of the FDG-MNPs.…”

“…25 Briefly, 12 mL of 2 M FeCl 3 (Fluka, Istanbul, Turkey) solution in 2 M HCl (Merck, Istanbul, Turkey) was added to a 500 mL three necked glass flask. 50 mL of a freshly prepared 80 mM Na 2 SO 3 (Merck) solution followed by 5 ml of NH 3 solution (25%) (Merck) added to the flask, both dropwise under nitrogen gas.…”

“…Previously, we observed a cell death rate of 72% in response to exposure to our FDG-MNPs in vitro without magnetic field stimulation. 25 Therefore, in the current study we assessed tissue tumour expression of several genes involved in apoptosis to define the in vivo impact of our FDG-MNPS on cell death.…”

“…We observed rapid and sustained hyperthermia, resulting in the death of 89% of MCF-7 cancer cells in vitro. 25 While these studies demonstrate the validity of using FDG-MNPs to target cancer cells in vitro, it is essential that their impact on non-cancerous tissue in vivo is established. Currently, morphological and gene expression analysis of tissues can be undertaken to understand cellular responses that may occur prior to observing changes at the histological level.…”

“…Central to the measurement of gene expression profiles is the use of semi-quantitative reverse transcription real-time PCR (RT-qPCR). 25 This technique is both sensitive enough to detect changes in gene expression at single cell resolution 26 and robust enough to validate genome-wide expression analyses such as microarray data. However, in order to determine the expression levels of any gene of interest, its expression must be normalised against that of a reference gene.…”