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

Abstract

Fluorodeoxyglucose-conjugated magnetic nanoparticles, designed to target cancer cells with high specificity when heated by an alternating magnetic field, could provide a low-cost, non-toxic treatment for cancer. However, it is essential that the in vivo impacts of such technologies on both tumour and healthy tissues are characterised fully. Profiling tissue gene expression by semi-quantitative reverse transcriptase real-time PCR can provide a sensitive measurement of tissue response to treatment. However, the accuracy of such analyses is dependent on the selection of stable reference genes. In this study, we determined the impact of fluorodeoxyglucose-conjugated magnetic nanoparticles on tumour and nontumour tissue gene expression and morphology in MAC16 adenocarcinoma established male NMRI mice. Mice received an injection of 8 mg/kg body weight fluorodeoxyglucose-conjugated magnetic nanoparticles either intravenously in to the tail vein, directly into the tumour or subcutaneously directly overlying the tumour. Tissues from mice were sampled between 70 minutes and 12 hours post injection. Using the bioinformatic geNorm tool, we established the stability of six candidate reference genes (Hprt, Pgk1, Ppib, Sdha, Tbp and Tuba); we observed Pgk1 and Ppib to be the most stable. We then characterised the expression profiles of several apoptosis genes of interest in our adenocarcinoma samples, observing differential expression in response to mode of administration and exposure duration. Using histological assessment and fluorescent TUNNEL staining, we observed no detrimental impact on either tumour or non-tumour tissue morphology or levels of apoptosis. These observations define the underlying efficacy of fluorodeoxyglucose-conjugated magnetic nanoparticles on tumour and non-tumour tissue morphology and gene expression, setting the basis for future studies.

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“…Overall, the structural properties of synthesized mNPs and FDG-mNPs are in line with findings from previous studies [7,14,15,16].…”

“…The modified mNPs were conjugated with nonradiactive F using NaF. mNPs and FDG-mNPs characterized similarly as described in our previous reports [10,14,15,16]. Briefly, the hydrodynamic diameter of mNPs or FDG-mNPs was measured using DLS.…”

Effects of Fluorodeoxyglucose Conjugated and Unconjugated Iron Oxide Magnetic Nanoparticles on Macrophages: a Pilot Study

“…It has been shown that FDGMNP have high affinity for MCF-7 breast cancer cells according to previous studies [11]. In a study conducted with another group, FDGMNPs were injected both intratumorally and intravenously (via the tail vein) in in-vivo studies on intraabdominal tumors of mice [16]. Mice were euthanized 70 minutes to 12 hours after injection.…”

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“…MNPs were synthesized, coated in silica, and fabricated with TEOS (tetraethyl orthosilicate). These modified MNPs were then conjugated with [ 19 F]FDG, optically labelled with ICG (indocyanine green) and characterized similarly as described in our previous reports [8,10,12,21].…”