Oncotarget

Research Papers:

Artesunate-modified nano-graphene oxide for chemo-photothermal cancer therapy

Yilin Pang, Zihao Mai, Bin Wang, Lu Wang, Liping Wu, Xiaoping Wang and Tongsheng Chen _

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Oncotarget. 2017; 8:93800-93812. https://doi.org/10.18632/oncotarget.21191

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Abstract

Yilin Pang1, Zihao Mai1, Bin Wang1, Lu Wang1, Liping Wu1, Xiaoping Wang2 and Tongsheng Chen1

1MOE Key Laboratory of Laser Life Science & College of Biophotonics, South China Normal University, Guangzhou 510631, PR China

2Department of Pain Management, The First Affiliated Hospital of Jinan University, Guangzhou 510630, PR China

Correspondence to:

Tongsheng Chen, email: chentsh@scnu.edu.cn, chentsh126@126.com

Xiaoping Wang, email: txp2938@jnu.edu.cn

Keywords: artesunate, nano-graphene oxide, chemo-photothermal synergistic therapy, peroxynitrite, near-infrared irradiation

Received: May 25, 2017     Accepted: August 26, 2017     Published: September 23, 2017

ABSTRACT

Poor water-solubility of artesunate (ARS) hampers its clinical application. We here covalently linked ARS to PEGylated nanographene oxide (nGO-PEG) to obtain ARS-modified nGO-PEG (nGO-PEG-ARS) with excellent photothermal effect and dispersibility in physiological environment. nGO-PEG-ARS induced reactive oxygen species (ROS) and peroxynitrite (ONOO) generations. Although nGO-PEG with near-infrared (NIR) irradiation did not induce cytotoxicity, the photothermal effect of nGO-PEG under NIR irradiation enhanced not only cell uptake but also ONOO generation of nGO-PEG-ARS, resulting in the synergistic chemo-photothermal effect of nGO-PEG-ARS in killing HepG2 cells. Pretreatment with Fe(III) 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato chloride (FeTTPS, a ONOO scavenger) instead of antioxidant N-Acetyle-Cysteine (NAC, an ROS scavenger) significantly blocked the cytotoxicity of nGO-PEG-ARS with or without NIR irradiation, demonstrating that ONOO instead of ROS dominated the synergistic chemo-photothermal anti-cancer action of nGO-PEG-ARS. nGO-PEG-ARS with NIR irradiation resulted in a complete tumor cure within 15 days earlier than other treatment groups, and did not induce apparent histological lesion for the mice treated with nGO-PEG-ARS with or without NIR irradiation for 30 days, further proving the synergistic chemo-photothermal anti-cancer effect of nGO-PEG-ARS. Collectively, nGO-PEG-ARS is a versatile nano-platform for multi-modal synergistic cancer therapy.


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