Gold nanoparticles enhance DNA damage induced by anti-cancer drugs and radiation.
The chemotherapeutic agent cisplatin was chemically linked to pGEM-3Zf(-) plasmid DNA to produce a cisplatin-DNA complex, Gold nanoparticles, which bind electrostatically to pure DNA, could also be added to this complex. Dry films of pure plasmid DNA and DNA-cisplatin, DNA-gold nanoparticles and DNA-cisplatin-gold nanoparticles complexes were bombarded by 60 keV electrons. The yields of single- and double-strand breaks were measured as a function of exposure by electrophoresis. From a comparison of such yields from the different type of films, we found that the binding of only one gold nanoparticle to a plasmid-cisplatin complex containing 3197 base pairs increases by a factor of 3 the efficiency of the chemotherapeutic agent cisplatin to produce double-strand breaks in irradiated DNA. Furthermore, adding two cisplatin molecules and one gold nanoparticle to DNA enhances radiation-induced DSBs by a factor of 7.5. A number of phenomena could contribute to this huge enhancement, including the higher density of low-energy electrons and reactive species around the gold nanoparticles and the weakening of bonds adjacent to cisplatin in the DNA backbone. The addition of gold nanoparticles to cisplatin and other platinum agents may therefore provide interesting avenues of research to improve the treatment of cancer by concomitant chemoradiation.
Zheng
Yi
Y
Groupe en sciences des radiations, Faculté de médecine, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.
Sanche
Léon
L
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D053904:DNA Breaks, Single-Stranded / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004270:DNA, Circular / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects; D044708:DNA, Concatenated / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects; D004278:DNA, Superhelical / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004583:Electrons; D004587:Electrophoresis, Agar Gel; D006046:Gold / Q000378:metabolism; D053768:Metal Nanoparticles; D009690:Nucleic Acid Conformation / Q000187:drug effects / Q000528:radiation effects; D010957:Plasmids / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects
D000970:Antineoplastic Agents; D004270:DNA, Circular; D044708:DNA, Concatenated; D004278:DNA, Superhelical; D006046:Gold; D004247:DNA; D002945:Cisplatin