Tissue morphology and gene expression characterisation of transplantable adenocarcinoma bearing mice exposed to fluorodeoxyglucose-conjugated magnetic nanoparticles

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

Research output: Contribution to journalArticle

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 8mg / 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.
Original languageEnglish
Pages (from-to)1979-1991
JournalJournal of Biomedical Nanotechnology
Volume14
Issue number11
Early online date30 Aug 2018
DOIs
Publication statusPublished - 1 Nov 2018

Bibliographical note

Copyright © 2018 American Scientific Publishers. This is an open access article.

Funding: Memorial Sloan Kettering Cancer Centre, Department of Radiology, and the NIH/NCI Cancer Center Support Grant P30 CA008748, USA. AJW is supported by an Aston Research Centre for Healthy Ageing (ARCHA) fellowship. OAk and OAs are supported by an MSK Cancer Center Support Grant/Core Grant (P30 CA008748).

Keywords

  • Apoptosis
  • gene expression
  • reference gene
  • magnetic nanoparticles
  • adenocarcinoma mouse model

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