The Synergistic Cytotoxic Effect of Laser-Irradiated Gold Nanoparticles and Sorafenib Against the Growth of a Human Hepatocellular Carcinoma Cell Line.

Haidy M Ebrahim,Mona E Morsy,Mahmoud N El-Rouby,Magda K Ezz,Mahmoud M Said

doi:10.31557/apjcp.2019.20.11.3369

Abstract

Gold nanoparticles are the most promising candidate in cancer treatment due to their physiochemical properties and increased use in photothermal therapy (PTT). In the present study, spherical gold nanoparticles (AuNPs) were synthesized using citrate reduction method. The particles were then characterized using UV-VIS spectroscopy and transmission electron microscope. A hepatocellular carcinoma cell line (HepG2) was incubated with sorafenib and/or non-irradiated or laser-irradiated AuNPs for 48 hrs. The cytotoxic effect of different treatment modalities was determined using MTT assay. Furthermore, apoptosis was determined by flow cytometry using annexin V/propidium iodide, as well as estimating the level of caspases. Results showed that AuNPs and sorafenib reduced HepG2 cell viability, and the cytotoxicity was associated with increased release of LDH in the culture medium. The recorded cytotoxicity was attributed to enhanced apoptosis as revealed by increased cellular caspases (3, 8 and 9), that was further confirmed by flow cytometry. The most notable cytotoxic effect was recorded when combining sorafenib with laser-irradiated AuNPs. In conclusion, a synergistic cytotoxic effect was observed between sorafenib and laser-irradiated AuNPs against the growth of HepG2, suggesting the potential substitution of large toxic doses of sorafenib by lower doses in combination with photothermal therapy.

Highlights

Hepatocellular carcinoma (HCC), one of the most aggressive forms of malignancies, is the sixth most common cancer and the fourth leading cause of cancer deaths worldwide, with approximately 782,000 deaths annually (Bray et al, 2018)
Results showed that AuNPs and sorafenib reduced HepG2 cell viability, and the cytotoxicity was associated with increased release of lactate dehydrogenase (LDH) in the culture medium
Therapeutic options in advanced irresectable HCC are limited to sorafenib, which is the available conventional chemotherapy for HCC treatment

Summary

Introduction

Hepatocellular carcinoma (HCC), one of the most aggressive forms of malignancies, is the sixth most common cancer and the fourth leading cause of cancer deaths worldwide, with approximately 782,000 deaths annually (Bray et al, 2018). This rising proportion of HCC can be attributed to increasing risk factors, including chronic infection with hepatitis B (HBV) or C (HCV) viruses, aflatoxin-contaminated food stuffs, heavy alcohol intake, obesity, smoking and type 2 diabetes. Plasmonic photothermal therapy (PPTT) is a non-invasive technique for the treatment of cancer, where laser irradiation causes oscillation of electrons in the conduction band of plasmonic nanoparticles, simultaneously absorbing and scattering the laser light and resulting in absorbed light conversion to heat that kills cancer cells (hyperthermia) through either activation of intrinsic or extrinsic apoptotic pathways (Bonzon et al, 2006; Ahmed et al, 2015; Wang et al, 2018)

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Results

Conclusion