Nanodiamonds improve arsenic trioxide treatment of liver tumor by inhibiting metastasis in multiple organs
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作者
Yan, Qinglong; Sun, Rui; Cui, Zhifen; Zhang, Jichao; Zhag, Yu; Zhang, Qi; Zhu, Shitai; Wang, Lihua; Li, Qian; Lu, Min; Zhu; Fan, Chunhai
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刊物名称
NANO TODAY
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年、卷、文献号
2022, 47, 1748-0132
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关键词
Yan, Qinglong; Sun, Rui; Cui, Zhifen; Zhang, Jichao; Zhag, Yu; Zhang, Qi; Zhu, Shitai; Wang, Lihua; Li, Qian; Lu, Min; Zhu; Fan, Chunhai
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摘要
Arsenic trioxide (ATO)-based therapy has demonstrated high potency in treating leukemia but limited ef-ficacy in solid tumors. Here we report a potent multiple organ-specific anti-metastatic mechanism of na-nodiamonds (NDs) in ATO-based therapy for liver cancer, which is characterized by its high metastatic potential that underlies the cause for cancer-related death. In a liver tumor mouse model, NDs co-treatment effectively inhibited the ATO-associated metastasis of liver cancer in the liver, spleen, and intestines, with inhibition potencies closely correlated with the biodistribution of NDs among different organs. Consequently, NDs co-treatment improved the survival rate of ATO-treated mice from 0% to 100% during 135-174 days from the initiation of therapy, with -20% survival of mice for over 10 months. Mechanistically, NDs co-treatment inhibited autophagy by upregulating LC3-II and p62, thereby inhibiting metastasis dissemination by inactivating the TGF-beta/Smad3 pathway. Our study unravels a potentially generalizable strategy for inhibiting multiple-organ cancer metastasis via nanoparticle-mediated mod-ulation of autophagy. (c) 2022 Elsevier Ltd. All rights reserved.
