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

Author:

Arya Braham D12,Mittal Sandeep23,Joshi Prachi1,Pandey Alok K23,Ramirez-Vick Jaime E4,Singh Surinder P12

Affiliation:

1. CSIR-National Physical Laboratory, Dr K. S. Krishnan Marg, New Delhi 110012, India

2. Academy of Scientific & Innovative Research (AcSIR), Sector 19, Ghaziabad, UP 201002, India

3. CSIR-Indian Institute of Toxicology Research (CSIR-IITR), 31, Mahatma Gandhi Marg, Lucknow 226001, India

4. Department of Biomedical, Industrial & Human Factors Engineering, Wright State University, Dayton, OH 45435, USA

Abstract

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.

Publisher

Future Medicine Ltd

Subject

Development,General Materials Science,Biomedical Engineering,Medicine (miscellaneous),Bioengineering

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