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

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 proposed to evaluate the radiosensitization effect in U87 glioblastoma (GBM) cells in the presence of 42 nm GNPs and irradiated with a clinical 6 MV photon beam. Cytotoxicity and radiosensitization was observed using MTS and clonogenic cellular radiation sensitivity assays respectively. Sensitization enhancement ratio was calculated for 2 Gy (SER2Gy) with GNP (100 μg/mL). Dark field and MTS assay revealed high co-localization and good biocompatibility of the GNPs with GBM cells. 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 GBM alone group (Mean (M) = 0.26, Standard Deviation (SD) = 0.008) and GBM plus GNP group (M = 0.07, SD = 0.05, P = 0.03). GNPs enable 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 standardise in-vitro model that can be employed for future studies involving metal nanoparticle plus irradiation.

Three-Dimensional Tumor Spheroids as a Tool for Reliable Investigation of Combined Gold Nanoparticle and Docetaxel Treatment

“…High atomic number noble metal nanoparticles (NPs), such as gold nanoparticles (GNPs; Z = 79) offer many advantages as a model nanomaterial-based system, such as bio-inertness and biostability, while also being simple to functionalize, proving beneficial in an in vivo environment [ 13 , 14 ]. GNPs have previously been shown to act as an effective radiosensitizer in clinically relevant energy ranges [ 15 , 16 , 17 ]. Targeting of GNPs to tumors can selectively increase deposited dose, increasing the therapeutic index [ 18 ].…”

Gold nanoparticles carrying or not anti-VEGF antibody do not change glioblastoma multiforme tumor progression in mice

“…Then, strategies to enhance the AuNP concentration in the glioblastoma and reduce the tumor size may include diminish the AuNP size, add different coverings, or include concomitant radiotherapy. In fact, it was demonstrated radiotherapy increases gold nanoparticles passage through the BBB, prolongs survival in mice carrying U251 glioma cells-induced tumor and enhances uptake of gold nanoparticles by tumor cells [ 40 , 56 ]. Further studies are needed to determine the effect of radiotherapy along with 20 nm cit-AuNP chronic treatment in the GL261-induced GBM in mice.…”

Novel Strategies for Nanoparticle-Based Radiosensitization in Glioblastoma

“…RT remains the primary treatment modality for unresectable GBM [ 40 , 41 ]. However, there are several drawbacks associated with this approach, including radioresistance due to tumor hypoxia, limitations in radiation dose due to normal tissue constraints, especially in the setting of previous radiation in recurrent tumors, and the lack of target specificity [ 42 , 43 , 44 ]. Therefore, it is clear that new approaches to improve the efficacy of radiation treatment for patients diagnosed with glioma are necessary.…”

“…In this setting, NP have been tested as radiosensitizing agents as well as carriers of other radiosensitizing agents, with studies demonstrating promising results after photon and particle radiation [ 44 , 46 , 47 ]. This strategy using nanomedicine aims to load NP with drugs that sensitize cancer cells to radiation, and thereby enhance the killing of residual disease and prevent treatment resistance [ 48 ].…”

“…Extensive preclinical studies have demonstrated significant local enhancement of the absorbed dose using AuNPs compared to kilovoltage (kV) X-rays alone. The impact of these structures is attributed to the photoelectric effect, resulting in a high mass energy coefficient relative to soft tissue [ 44 , 53 ]. Kazmi et al evaluated the radiosensitization effect on U87 GBM cells in the presence of 42 nm AuNPs and irradiated with clinical 6 MV photon beam.…”