Abstract

AbstractWe investigated the combinatorial cytotoxic actions of the chemotherapeutic drug (sorafenib tosylate, ST), in synergism with γ-radiation, on human hepatocellular carcinoma (HepG2) cells. The novel radiosensitizer, hexagonal gold nanoparticles (HG), was prepared and utilized to enhance the radiobiological response of HepG2 cells. A well-designed nanoporous alginate/calcium carbonate hybrid (ALG-CaCO3) was prepared as a biocompatible/biodegradable nanocarrier for co-delivery of the hydrophobic drug (ST) and the hydrophilic radiosensitizer (HG) to the cancer cells. Incubation of HepG2 cells with the prepared nanoprobes followed by irradiation with different doses (0, 3 or 6 Gy) of γ-radiation resulted in a significant reduction of the cells viability as a result of the synergistic (chemo-radiation) cytotoxic actions.

Highlights

  • Nanotechnology provides several methods for physical encapsulation of hydrophilic and/or hydrophobic drugs in biocompatible polymers in mild conditions [1]

  • Hexagonal gold nanoparticles were prepared and used as a novel radiosensitizer to enhance the radiobiological response of HepG2 cells

  • This study aims to investigate the cytotoxic actions of gold hexagons-sensitized radiation in synergism with sorafenib tosylate against human hepatoma HepG2 cells

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Summary

Introduction

Nanotechnology provides several methods for physical encapsulation of hydrophilic and/or hydrophobic drugs in biocompatible polymers in mild conditions [1]. The low bioavailability, hepatic first path and cell resistivity are the main challenges towards achieving high potency of ST in the clinical therapy [7] To address such issues, many approaches have been developed such as incorporation of ST in nanoparticles made of biodegradable polymers [8, 9]. The low energy and short effective zone of Auger electrons lead to deposition of energy around the nanoparticles localized at the tumor sites [14] Radiosensitizers, such as gold nanoparticles, improve the response of hypoxic tumor cells to the ionizing radiation even at low radiation doses [15]. This is mainly attributed to their strong photoelectric absorption coefficient [16]. The proposed combinatorial model (HG-ST-ALG in synergism with γ-radiation) is promising for effective and minimally invasive treatment of HepG2 cells

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