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

被引：103

作者：

Cui, Zhifen ^{[1
]}

Zhang, Yu ^{[1
]}

Xia, Kai ^{[1
]}

Yan, Qinglong ^{[1
]}

Kong, Huating ^{[1
]}

Zhang, Jichao ^{[1
]}

Zuo, Xiaolei ^{[2
]}

Shi, Jiye ^{[1
,3
]}

Wang, Lihua ^{[1
,4
]}

Zhu, Ying ^{[1
]}

Fan, Chunhai ^{[1
,2
]}

机构：

[1] Univ Chinese Acad Sci, Shanghai Synchrotron Radiat Facil, Shanghai Inst Appl Phys, Chinese Acad Sci,Div Phys Biol & Bioimaging Ctr, Shanghai 201800, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Chem & Chem Engn, Renji Hosp, Inst Mol Med,Sch Med, Shanghai 200240, Peoples R China

[3] Univ Oxford, Kellogg Coll, Banbury Rd, Oxford OX2 6PN, England

[4] East China Normal Univ, Sch Chem & Mol Engn, Shanghai Key Lab Green Chem & Chem Proc, 500 Dongchuan Rd, Shanghai 200241, Peoples R China

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

中国国家自然科学基金;

关键词：

ACUTE PROMYELOCYTIC LEUKEMIA; CELL-DEATH; CANCER; TRIOXIDE; APOPTOSIS; HYDROXYCHLOROQUINE; CHLOROQUINE; CARCINOMA; DRUGS; MODEL;

D O I：

10.1038/s41467-018-06749-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 similar to 91% carcinoma decrease as compared with similar to 28% without NDs. Treated mice show 100% survival rate in 150 days with greatly reduced advanced liver carcinoma-associated symptoms, and similar to 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.

引用

页数：11

共 43 条

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