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Modulation of Hypoxia by Magnetic Nanoparticle Hyperthermia to Augment Therapeutic Index

  • Eunice Y. Chen
  • Kimberley S. Samkoe
  • Sassan Hodge
  • Katherine Tai
  • Huagang Hou
  • Alicia A. Petryk
  • Rendall Strawbridge
  • P. Jack Hoopes
  • Nadeem Khan
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 812)

Abstract

A hypoxic microenvironment in solid tumors has been known to cause resistance to standard therapies and to increase the malignant potential of tumors. The utilization of magnetic nanoparticle hyperthermia (mNPH) has shown promise in improving therapeutic outcome by (1) killing of hypoxic tumor cells directly and (2) increasing tumor oxygenation and therefore susceptibility to therapies. In this study, the interaction of a hypoxic microenvironment with mNPH efficacy was investigated in a human breast cancer orthotopic xenograft model. Using electron paramagnetic resonance (EPR) to assess in vivo oxygen concentration in tumors repeatedly and non-invasively, we found that mNPH increased tumor pO2 from 3.5 to 68.8 mmHg on average for up to 10 days. Tumors treated once with mNPH showed growth delay. On Transmission Electron Microscopy, magnetic nanoparticles (mNPs) were localized intracellularly in multiple vesicles in the cytoplasm of cells within tumors 48 h after incubation of mNP. In conclusion, mNPH increased tumor oxygenation in vivo and resulted in decreased growth of hypoxic tumors. Future studies will establish tumor pO2-guided multimodal therapies, such as mNPH and radiation, to improve therapeutic efficacy.

Keywords

Tumor hypoxia Magnetic nanoparticle hyperthermia (mNPH) Electron paramagnetic resonance (EPR) oximetry 

Notes

Acknowledgments

This study is supported by the Dartmouth Center for Cancer Nanotechnology Excellence (DCCNE) and Dartmouth Center for Clinical and Translational Sciences (Synergy) Pilot Grants.

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Copyright information

© Springer Science+Business Media, LLC 2014

Authors and Affiliations

  • Eunice Y. Chen
    • 1
    • 2
  • Kimberley S. Samkoe
    • 1
    • 3
    • 4
  • Sassan Hodge
    • 1
    • 3
  • Katherine Tai
    • 5
  • Huagang Hou
    • 6
  • Alicia A. Petryk
    • 4
  • Rendall Strawbridge
    • 1
    • 3
  • P. Jack Hoopes
    • 1
    • 3
    • 4
  • Nadeem Khan
    • 6
  1. 1.Department of SurgeryGeisel School of MedicineHanoverUSA
  2. 2.Section of Otolaryngology–Head and Neck Surgery, Department of SurgeryDartmouth Hitchcock Medical CenterLebanonUSA
  3. 3.Department of SurgeryDartmouth Hitchcock Medical CenterLebanonUSA
  4. 4.Thayer School of Engineering, Dartmouth CollegeHanoverUSA
  5. 5.Dartmouth CollegeHanoverUSA
  6. 6.Department of RadiologyGeisel School of MedicineHanoverUSA

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