Ultrasmall glutathione-protected gold nanoclusters as next generation radiotherapy sensitizers with high tumor uptake and high renal clearance.
Radiotherapy is often the most straightforward first line cancer treatment for solid tumors. While it is highly effective against tumors, there is also collateral damage to healthy proximal tissues especially with high doses. The use of radiosensitizers is an effective way to boost the killing efficacy of radiotherapy against the tumor while drastically limiting the received dose and reducing the possible damage to normal tissues. Here, we report the design and application of a good radiosensitizer by using ultrasmall Au(29-43)(SG)(27-37) nanoclusters (<2 nm) with a naturally-occurring peptide (e.g., glutathione or GSH) as the protecting shell. The GSH-coated Au(29-43)(SG)(27-37) nanoclusters can escape the RES absorption, leading to a good tumor uptake (~8.1% ID/g at 24 h post injection). As a result, the as-designed Au nanoclusters led to a strong enhancement for radiotherapy, as well as a negligible damage to normal tissues. After the treatment, the ultrasmall Au(29-43)(SG)(27-37) nanoclusters can be efficiently cleared by the kidney, thereby avoiding potential long-term side-effects caused by the accumulation of gold atoms in the body. Our data suggest that the ultrasmall peptide-protected Au nanoclusters are a promising radiosensitizer for cancer radiotherapy.
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 238, Baidi Road, Tianjin. 300192, China.
Xiao-Dong
XD
Zhang
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
Zhentao
Z
Luo
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 238, Baidi Road, Tianjin. 300192, China.
Jie
J
Chen
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 238, Baidi Road, Tianjin. 300192, China.
Shasha
S
Song
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
Xun
X
Yuan
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 238, Baidi Road, Tianjin. 300192, China.
Xiu
X
Shen
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 238, Baidi Road, Tianjin. 300192, China.
Hao
H
Wang
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 238, Baidi Road, Tianjin. 300192, China.
Yuanming
Y
Sun
Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences &Comparative Medical Center, Peking Union Medical College, Beijing. 100021, China.
Kai
K
Gao
Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences &Comparative Medical Center, Peking Union Medical College, Beijing. 100021, China.
Lianfeng
L
Zhang
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 238, Baidi Road, Tianjin. 300192, China.
Saijun
S
Fan
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
David Tai
DT
Leong
Department of Physics, School of Science, Tianjin Chengjian University, Tianjin 300384, China.
Meili
M
Guo
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
Jianping
J
Xie
D000818:Animals; D005978:Glutathione / Q000097:blood; D006046:Gold / Q000097:blood / Q000627:therapeutic use*; D057446:Hydrodynamics; D021621:Imaging, Three-Dimensional; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D053768:Metal Nanoparticles / Q000627:therapeutic use* / Q000648:ultrastructure; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden / Q000187:drug effects
D011838:Radiation-Sensitizing Agents; D006046:Gold; D005978:Glutathione