Cell type-dependent uptake, localization, and cytotoxicity of 1.9 nm gold nanoparticles.
BACKGROUND
This follow-up study aims to determine the physical parameters which govern the differential radiosensitization capacity of two tumor cell lines and one immortalized normal cell line to 1.9 nm gold nanoparticles. In addition to comparing the uptake potential, localization, and cytotoxicity of 1.9 nm gold nanoparticles, the current study also draws on comparisons between nanoparticle size and total nanoparticle uptake based on previously published data.


METHODS
We quantified gold nanoparticle uptake using atomic emission spectroscopy and imaged intracellular localization by transmission electron microscopy. Cell growth delay and clonogenic assays were used to determine cytotoxicity and radiosensitization potential, respectively. Mechanistic data were obtained by Western blot, flow cytometry, and assays for reactive oxygen species.


RESULTS
Gold nanoparticle uptake was preferentially observed in tumor cells, resulting in an increased expression of cleaved caspase proteins and an accumulation of cells in sub G(1) phase. Despite this, gold nanoparticle cytotoxicity remained low, with immortalized normal cells exhibiting an LD(50) concentration approximately 14 times higher than tumor cells. The surviving fraction for gold nanoparticle-treated cells at 3 Gy compared with that of untreated control cells indicated a strong dependence on cell type in respect to radiosensitization potential.


CONCLUSIONS
Gold nanoparticles were most avidly endocytosed and localized within cytoplasmic vesicles during the first 6 hours of exposure. The lack of significant cytotoxicity in the absence of radiation, and the generation of gold nanoparticle-induced reactive oxygen species provide a potential mechanism for previously reported radiosensitization at megavoltage energies.
School of Pharmacy, McClay Research Centre, Queens University Belfast, Belfast, Ireland. j.coulter@qub.ac.uk
Jonathan A
JA
Coulter
Suneil
S
Jain
Karl T
KT
Butterworth
Laura E
LE
Taggart
Glenn R
GR
Dickson
Stephen J
SJ
McMahon
Wendy B
WB
Hyland
Mark F
MF
Muir
Coleman
C
Trainor
Alan R
AR
Hounsell
Joe M
JM
O'Sullivan
Giuseppe
G
Schettino
Fred J
FJ
Currell
David G
DG
Hirst
Kevin M
KM
Prise
D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D006046:Gold / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013054:Spectrophotometry, Atomic; D018675:Toxicity Tests
D051017:Apoptosis Regulatory Proteins; D017382:Reactive Oxygen Species; D006046:Gold