Targeted iron oxide nanoparticles for the enhancement of radiation therapy

Anastasia K. Hauser, Mihail I. Mitov, Emily F. Daley, Ronald C. McGarry, Kimberly W. Anderson, J. Zach Hilt

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

To increase the efficacy of radiation, iron oxide nanoparticles can be utilized for their ability to produce reactive oxygen species (ROS). Radiation therapy promotes leakage of electrons from the electron transport chain and leads to an increase in mitochondrial production of the superoxide anion which is converted to hydrogen peroxide by superoxide dismutase. Iron oxide nanoparticles can then catalyze the reaction from hydrogen peroxide to the highly reactive hydroxyl radical. Therefore, the overall aim of this project was to utilize iron oxide nanoparticles conjugated to a cell penetrating peptide, TAT, to escape lysosomal encapsulation after internalization by cancer cells and catalyze hydroxyl radical formation. It was determined that TAT functionalized iron oxide nanoparticles and uncoated iron oxide nanoparticles resulted in permeabilization of the lysosomal membranes. Additionally, mitochondrial integrity was compromised when A549 cells were treated with both TAT-functionalized nanoparticles and radiation. Pre-treatment with TAT-functionalized nanoparticles also significantly increased the ROS generation associated with radiation. A long term viability study showed that TAT-functionalized nanoparticles combined with radiation resulted in a synergistic combination treatment. This is likely due to the TAT-functionalized nanoparticles sensitizing the cells to subsequent radiation therapy, because the nanoparticles alone did not result in significant toxicities.

Original languageEnglish
Pages (from-to)127-135
Number of pages9
JournalBiomaterials
Volume105
DOIs
StatePublished - Oct 1 2016

Bibliographical note

Funding Information:
This research was supported by the Redox Metabolism (RM) Shared Resource Facility (SRF) of the University of Kentucky Markey Cancer Center ( P30CA177558 ). The project described was partially supported by Grant Number R25CA153954 from the National Cancer Institute . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Additionally, this work was supported by the National Science Foundation Graduate Research Fellowship Program Grant No. DGE-1247392 . Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

Publisher Copyright:
© 2016 Elsevier Ltd

Keywords

  • Cell penetrating peptide
  • Iron oxide nanoparticles
  • Radiation
  • Reactive oxygen species
  • Seahorse mitochondrial stress test

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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