Graphene oxide-chloroquine nanoconjugate induce necroptotic death in A549 cancer cells through autophagy modulation

被引:45
作者
Arya, Braham D. [1 ,2 ]
Mittal, Sandeep [2 ,3 ]
Joshi, Prachi [1 ]
Pandey, Alok K. [2 ,3 ]
Ramirez-Vick, Jaime E. [4 ]
Singh, Surinder P. [1 ,2 ]
机构
[1] CSIR Natl Phys Lab, Dr KS Krishnan Marg, New Delhi 110012, India
[2] AcSIR, Sect 19, Ghaziabad 201002, UP, India
[3] CSIR IITR, 31 Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India
[4] Wright State Univ, Dept Biomed Ind & Human Factors Engn, Dayton, OH 45435 USA
关键词
A549; autophagosomes; autophagy; cancer therapy; chloroquine; endocytosis; graphene oxide; lysosome; nanoconjugate; necroptosis; WALLED CARBON NANOTUBES; MOLECULAR-MECHANISMS; PROGRAMMED NECROSIS; IN-VITRO; MITOCHONDRIAL DAMAGE; GRAPHITE OXIDE; DRUG-DELIVERY; APOPTOSIS; THERAPY; STRESS;
D O I
10.2217/nnm-2018-0086
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Aim: Chloroquine (Chl) has shown its potential in cancer therapy and graphene oxide (GO) exhibited excellent tumor-targeting ability, biocompatibility and low toxicity. We have endeavored to conjugate Chl to GO sheets and investigated the nonproliferation action on A549 cell lines along with cell signaling pathways. Materials & methods: Cellular toxicity, autophagic flux modulation and cell death mechanism induced by GO-Chl have been investigated on A549 cell lines. Results & conclusion: GO-Chl induces accumulation of autophagosomes (monodansylcadaverine staining, green fluorescence protein-tagged LC3 plasmid and transmission electron microscopy observations) in A549 cells through the blockade of autophagic flux that serves as scaffold for necrosome assembling and activates necroptotic cell death. GO-Chl nanoconjugate could be used as an effective cancer therapeutic agent, by targeting the autophagy necroptosis axis.
引用
收藏
页码:2261 / 2282
页数:22
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