Nanodiamond autophagy inhibitor allosterically improves the arsenical-based therapy of solid tumors

Zhifen Cui, Yu Zhang, Kai Xia, Qinglong Yan, Huating Kong, Jichao Zhang, Xiaolei Zuo, Jiye Shi, Lihua Wang (), Ying Zhu () and Chunhai Fan ()
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Zhifen Cui: University of Chinese Academy of Sciences
Yu Zhang: University of Chinese Academy of Sciences
Kai Xia: University of Chinese Academy of Sciences
Qinglong Yan: University of Chinese Academy of Sciences
Huating Kong: University of Chinese Academy of Sciences
Jichao Zhang: University of Chinese Academy of Sciences
Xiaolei Zuo: Shanghai Jiao Tong University
Jiye Shi: University of Chinese Academy of Sciences
Lihua Wang: University of Chinese Academy of Sciences
Ying Zhu: University of Chinese Academy of Sciences
Chunhai Fan: University of Chinese Academy of Sciences

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract Arsenic trioxide (ATO) is a successful chemotherapeutic drug for blood cancers via selective induction of apoptosis; however its efficacy in solid tumors is limited. Here we repurpose nanodiamonds (NDs) as a safe and potent autophagic inhibitor to allosterically improve the therapeutic efficacy of ATO-based treatment in solid tumors. We find that NDs and ATO are physically separate and functionally target different cellular pathways (autophagy vs. apoptosis); whereas their metabolic coupling in human liver carcinoma cells remarkably enhances programmed cell death. Combination therapy in liver tumor mice model results in ~91% carcinoma decrease as compared with ~28% without NDs. Treated mice show 100% survival rate in 150 days with greatly reduced advanced liver carcinoma-associated symptoms, and ~80% of post-therapy mice survive for over 20 weeks. Our work presents a novel strategy to harness the power of nanoparticles to broaden the scope of ATO-based therapy and more generally to fight solid tumors.

Date: 2018
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DOI: 10.1038/s41467-018-06749-2

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