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

Julian Wong,Oguz Akin,Ozge K Guldu,Volkan Yasakci,Omer Aras,Gillian Pearce,Adam J Watkins,Xianghong Ma,Perihan Unak

doi:10.1166/jbn.2018.2631

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 non-tumour 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.

Highlights

Despite decades of research and significant financial investment, a definitive treatment or cure for cancer remains elusive
Stimulated state on tumour and non-tumour tissue in mice. One such approach is though the synthesis and surface bearing MAC16 adenocarcinomas in a non-magnetic field modification of magnetic nanoparticles (MNPs)
Mice of reference genes needed for any analysis of gene expreswere left for up to 12 hours prior to analysis of tissue morphology, ICG-labelled FDG-MNP tissue distribution and apoptosis pathway gene expression

Summary

Introduction

Despite decades of research and significant financial investment, a definitive treatment or cure for cancer remains elusive. 72% in response to exposure to our FDG-MNPs in vitro without magnetic field stimulation.[25] 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.

Objectives

Results

Conclusion