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

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

doi:10.18632/oncotarget.21191

Xiaoping Wang, Yilin Pang + Show 5 more

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https://doi.org/10.18632/oncotarget.21191

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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.

Highlights

Nanoparticle therapeutics has been demonstrated to be a potential multi-modal approach to enhance efficacy and simultaneously reduce side effects of cancer treatment [1,2,3]
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 reactive oxygen species (ROS) scavenger) significantly blocked the cytotoxicity of Nano-graphene oxide (nGO)-Polyethylene glycol (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
In the Fourier transfer infrared (FT-IR) spectrum, most absorption peaks of OH (~3425 cm-1), C=O (~1726 cm-1), C=C (~1575 cm-1) and C-O (~1059 cm1) are the functional groups of the carboxylated nGO [39, 40], and obvious CH2 (~2900 cm-1) and C-O-C (~1100 cm1) stretching vibrations are the functional groups of PEG [41], which appeared in the FTIR spectrum of nGOPEG with only a slight shift of peak positions and change of relative intensity (Figure 1D), indicating the successful synthesis of nGO-PEG

Summary

Introduction

Nanoparticle therapeutics has been demonstrated to be a potential multi-modal approach to enhance efficacy and simultaneously reduce side effects of cancer treatment [1,2,3]. NGO has ultrahigh loading capacity of aromatic drugs due to its large specific surface area and the strong non-covalent binding (hydrophobic interactions and π-π stacking) between aromatic molecules and aromatic regions of nGO [23,24,25]. Yang and colleagues reported that nGO loaded doxorubicin (DOX) as high as 235% (the weight ratio of loaded drug to carriers) by π-π stacking and hydrophobic interactions [26]. Zhang and colleagues developed DOXloaded nGO-PEG to combine chemotherapy and PTT in one system, which significantly improved the therapeutic efficacy of mammary cancer treatment in in vivo and in vitro [17]. We recently synthetized noncovalently PEGylated nrGO (nrGO/PEG) loading about 175.6 w/w % of resveratrol (RV) via π-π and hydrophobic interactions and exhibiting dramatically synergistic anti-cancer effect of PTT and chemotherapy in vitro and in vivo [28]

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