Gold nanoparticle cellular uptake, toxicity and radiosensitisation in hypoxic conditions.
OBJECTIVE
Gold nanoparticles (GNPs) are novel agents that have been shown to cause radiosensitisation in vitro and in vivo. Tumour hypoxia is associated with radiation resistance and reduced survival in cancer patients. The interaction of GNPs with cells in hypoxia is explored.


METHODS
GNP uptake, localization, toxicity and radiosensitisation were assessed in vitro under oxic and hypoxic conditions.


RESULTS
GNP cellular uptake was significantly lower under hypoxic than oxic conditions. A significant reduction in cell proliferation in hypoxic MDA-MB-231 breast cancer cells exposed to GNPs was observed. In these cells significant radiosensitisation occurred in normoxia and moderate hypoxia. However, in near anoxia no significant sensitisation occurred.


CONCLUSIONS
GNP uptake occurred in hypoxic conditions, causing radiosensitisation in moderate, but not extreme hypoxia in a breast cancer cell line. These findings may be important for the development of GNPs for cancer therapy.
Centre for Cancer Research and Cell Biology, School of Medicine, Queen's University Belfast, United Kingdom. Electronic address: s.jain@qub.ac.uk.
Suneil
S
Jain
Experimental Therapeutics Research Group, School of Pharmacy, Queen's University Belfast, United Kingdom.
Jonathan A
JA
Coulter
Centre for Cancer Research and Cell Biology, School of Medicine, Queen's University Belfast, United Kingdom.
Karl T
KT
Butterworth
Medical Physics Agency, Northern Ireland Cancer Centre, Belfast, United Kingdom.
Alan R
AR
Hounsell
Centre for Cancer Research and Cell Biology, School of Medicine, Queen's University Belfast, United Kingdom.
Stephen J
SJ
McMahon
Medical Physics Agency, Northern Ireland Cancer Centre, Belfast, United Kingdom.
Wendy B
WB
Hyland
Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, United Kingdom.
Mark F
MF
Muir
Centre for Cancer Research and Cell Biology, School of Medicine, Queen's University Belfast, United Kingdom.
Glenn R
GR
Dickson
Centre for Cancer Research and Cell Biology, School of Medicine, Queen's University Belfast, United Kingdom.
Kevin M
KM
Prise
Centre for Plasma Physics, School of Mathematics and Physics, Queen's University Belfast, United Kingdom.
Fred J
FJ
Currell
Experimental Therapeutics Research Group, School of Pharmacy, Queen's University Belfast, United Kingdom.
David G
DG
Hirst
Centre for Cancer Research and Cell Biology, School of Medicine, Queen's University Belfast, United Kingdom.
Joe M
JM
O'Sullivan
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D048708:Cell Growth Processes / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D006046:Gold / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000633:toxicity; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity
D011838:Radiation-Sensitizing Agents; D006046:Gold
Gold nanoparticles; Hypoxia; Radiosensitisers; Toxicity