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

作者：Pang, Yilin; Mai, Zihao; Wang, Bin; Wang, Lu; Wu, Liping; Wang, Xiaoping^*; Chen, Tongsheng^*

来源：Oncotarget, 2017, 8(55): 93800-93812.

DOI：10.18632/oncotarget.21191

• artesunate
• nano-graphene oxide
• chemo-photothermal synergistic therapy
• peroxynitrite
• near-infrared irradiation

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 anticancer effect of nGO-PEG-ARS. Collectively, nGO-PEG-ARS is a versatile nano-platform for multi-modal synergistic cancer therapy.

• 出版日期2017-11-7
• 单位暨南大学