Gold nanoparticles as radiation sensitizers in cancer therapy.
Among other nanoparticle systems, gold nanoparticles have been explored as radiosensitizers. While most of the research in this area has focused on either gold nanoparticles with diameters of less than 2 nm or particles with micrometer dimensions, it has been shown that nanoparticles 50 nm in diameter have the highest cellular uptake. We present the results of in vitro studies that focus on the radiosensitization properties of nanoparticles in the size range from 14-74 nm. Radiosensitization was dependent on the number of gold nanoparticles internalized within the cells. Gold nanoparticles 50-nm in diameter showed the highest radiosensitization enhancement factor (REF) (1.43 at 220 kVp) compared to gold nanoparticles of 14 and 74 nm (1.20 and 1.26, respectively). Using 50-nm gold nanoparticles, the REF for lower- (105 kVp) and higher- (6 MVp) energy photons was 1.66 and 1.17, respectively. DNA double-strand breaks were quantified using radiation-induced foci of gamma-H2AX and 53BP1, and a modest increase in the number of foci per nucleus was observed in irradiated cell populations with internalized gold nanoparticles. The outcome of this research will enable the optimization of gold nanoparticle-based sensitizers for use in therapy.
STTARR Innovation Centre, University Health Network, Toronto, Ontario, Canada. devika.chithrani@rmp.uhn.on.ca
Devika B
DB
Chithrani
Salomeh
S
Jelveh
Farid
F
Jalali
Monique
M
van Prooijen
Christine
C
Allen
Robert G
RG
Bristow
Richard P
RP
Hill
David A
DA
Jaffray
D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D006046:Gold / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D053768:Metal Nanoparticles; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D010316:Particle Size; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000071857:Tumor Suppressor p53-Binding Protein 1; D014964:X-Ray Therapy
C468783:H2AX protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D011838:Radiation-Sensitizing Agents; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D006046:Gold