Megavoltage Radiosensitization of Gold Nanoparticles on a Glioblastoma Cancer Cell Line Using a Clinical Platform.

Farasat Kazmi,Duan Yukun,Katherine A Vallis,Robert Carlisle,Aishwarya Bandla,Balamurugan A Vellayappan

doi:10.3390/ijms21020429

Abstract

Gold nanoparticles (GNPs) have demonstrated significant dose enhancement with kilovoltage (kV) X-rays; however, recent studies have shown inconsistent findings with megavoltage (MV) X-rays. We propose to evaluate the radiosensitization effect on U87 glioblastoma (GBM) cells in the presence of 42 nm GNPs and irradiated with a clinical 6 MV photon beam. Cytotoxicity and radiosensitization were measured using MTS and clonogenic cellular radiation sensitivity assays, respectively. The sensitization enhancement ratio was calculated for 2 Gy (SER2Gy) with GNP (100 μg/mL). Dark field and MTS assays revealed high co-localization and good biocompatibility of the GNPs with GBM cells. A significant sensitization enhancement of 1.45 (p = 0.001) was observed with GNP 100 μg/mL. Similarly, at 6 Gy, there was significant difference in the survival fraction between the GBM alone group (mean (M) = 0.26, standard deviation (SD) = 0.008) and the GBM plus GNP group (M = 0.07, SD = 0.05, p = 0.03). GNPs enabled radiosensitization in U87 GBM cells at 2 Gy when irradiated using a clinical platform. In addition to the potential clinical utility of GNPs, these studies demonstrate the effectiveness of a robust and easy to standardize an in-vitro model that can be employed for future studies involving metal nanoparticle plus irradiation.

Highlights

Glioblastoma (GBM) is one of the most common and aggressive brain cancers in adults, affecting 3 in 100,000 individuals worldwide annually [1]
The primary aim of this study is to investigate the radiosensitization effects of Gold nanoparticles (GNPs) on U87 human glioblastoma (GBM) cells using a 6 MV X-ray generated via the use of an easy to establish and standardized clinical linear accelerator (LINAC)
A zeta potential of −42.03 mV further confirmed that GNPs in this sample were electrically stable, ensuring good colloidal dispersion

Summary

Introduction

Glioblastoma (GBM) is one of the most common and aggressive brain cancers in adults, affecting 3 in 100,000 individuals worldwide annually [1]. A major appeal of nanoparticles (NPs) is their ability to deliver cytotoxic agents to the tumor site with increased precision and effectiveness via a phenomenon known as the enhanced permeability and retention effect (EPR) [4]. Dorsey’s group demonstrated a dose enhancement of 30% with 13 nm GNPs incubated in U251 GBM cells when targeted with a 150 kV X-ray [11]. These findings have been further validated with existing in vitro and in vivo experiments using different cancer cell lines [12,13]. Using an in vivo mouse model, he demonstrated tumor regression by approximately 35% compared to RT alone [14]

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Methods

Results