Size-dependent radiosensitization of PEG-coated gold nanoparticles for cancer radiation therapy.
Gold nanoparticles have been conceived as a radiosensitizer in cancer radiation therapy, but one of the important questions for primary drug screening is what size of gold nanoparticles can optimally enhance radiation effects. Herein, we perform in vitro and in vivo radiosensitization studies of 4.8, 12.1, 27.3, and 46.6 nm PEG-coated gold nanoparticles. In vitro results show that all sizes of the PEG-coated gold nanoparticles can cause a significant decrease in cancer cell survival after gamma radiation. 12.1 and 27.3 nm PEG-coated gold nanoparticles have dispersive distributions in the cells and stronger sensitization effects than 4.8 and 46.6 nm particles by both cell apoptosis and necrosis. Further, in vivo results also show all sizes of the PEG-coated gold nanoparticles can significantly decrease tumor volume and weight after 5 Gy radiations, and 12.1 and 27.3 nm PEG-coated gold nanoparticles have greater sensitization effects than 4.8 and 46.6 nm particles, which can lead to almost complete disappearance of the tumor. In vivo biodistribution confirms that 12.1 and 27.3 nm PEG-coated gold nanoparticles are accumulated in the tumor with high concentrations. The pathology, immune response, and blood biochemistry indicate that the PEG-coated gold nanoparticles have not caused spleen and kidney damages, but give rise to liver damage and gold accumulation. It can be concluded that 12.1 and 27.3 nm PEG-coated gold nanoparticles show high radiosensitivity, and these results have an important indication for possible radiotherapy and drug delivery.
Institute of Radiation Medicine and Tianjin Key Laboratory of Molecular Nuclear Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, People's Republic of China. Xiaodongzhang@tju.edu.cn
Xiao-Dong
XD
Zhang
Di
D
Wu
Xiu
X
Shen
Jie
J
Chen
Yuan-Ming
YM
Sun
Pei-Xun
PX
Liu
Xing-Jie
XJ
Liang
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006046:Gold / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000473:pathology; D053768:Metal Nanoparticles / Q000627:therapeutic use* / Q000633:toxicity / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D009929:Organ Size / Q000187:drug effects; D010316:Particle Size; D010949:Plasma; D011092:Polyethylene Glycols / Q000737:chemistry*; D011836:Radiation Tolerance / Q000187:drug effects; D014018:Tissue Distribution / Q000187:drug effects
D011092:Polyethylene Glycols; D006046:Gold