Modulation of hypoxia by magnetic nanoparticle hyperthermia to augment therapeutic index.
Adv Exp Med Biol
; 812: 87-95, 2014.
Article
em En
| MEDLINE
| ID: mdl-24729219
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Hipóxia Celular
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Nanopartículas
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Hipertermia Induzida
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Magnetismo
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Adv Exp Med Biol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos