Megavoltage Radiosensitization of Gold Nanoparticles on a 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 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.

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.…”

Nanoparticles for Stem Cell Therapy Bioengineering in Glioma

“…2019; Shi et al, 2019;Sousa et al, 2019;Ye et al, 2019;Zhang et al, 2019;Zhao et al, 2019;ZhuGe et al, 2019;Alves et al, 2020;Caban-Toktas et al, 2020;Chung et al, 2020;Ferreira et al, 2020;Kazmi et al, 2020;Liang et al, 2020;Martinez-Rovira et al, 2020;Meng et al, 2020;Roberts et al, 2020;Ullah et al, 2020;Wang H. et al, 2020;Wang X. et al, 2020;Xu et al, 2020;Zhu et al, 2020; see Table 3 for examples of ligand targeting in glioma research). Another active targeting method to increase functional specificity of NPs that are used as gene delivery systems is the transcriptional targeting, which can occur at a transcriptional or posttranscriptional level (Golombek et al, 2018).…”

“…Active targeting is achieved by different methods; a method called ligand targeting works by coating the nanoparticles’ surface with one or more ligands such as transferrin, epidermal growth factor (EGF), folic acid, arginyl-glycyl-aspartic tripeptide (RGD) peptide, hyaluronic acid, antibodies, and others ( Ruiz-Garcia et al, 2020 ). These ligands allow NPs to bind specific “receptors” differentially expressed only in certain cancerous blood vessels and/or tumor cells, thus leading to a precise cellular internalization ( Maier-Hauff et al, 2007 ; Kim et al, 2010 ; Wegscheid et al, 2014 ; Cheng Y. et al, 2016 ; Shen et al, 2017 ; Yu et al, 2017 , 2019 ; Hua et al, 2018 ; Daniel et al, 2019 ; Denora et al, 2019 ; Dufort et al, 2019 ; Kefayat et al, 2019 ; Kunoh et al, 2019 ; Luque-Michel et al, 2019 ; Rego et al, 2019 , 2020 ; Ruan et al, 2019 ; Shi et al, 2019 ; Sousa et al, 2019 ; Ye et al, 2019 ; Zhang et al, 2019 ; Zhao et al, 2019 ; ZhuGe et al, 2019 ; Alves et al, 2020 ; Caban-Toktas et al, 2020 ; Chung et al, 2020 ; Ferreira et al, 2020 ; Kazmi et al, 2020 ; Liang et al, 2020 ; Martinez-Rovira et al, 2020 ; Meng et al, 2020 ; Roberts et al, 2020 ; Ullah et al, 2020 ; Wang H. et al, 2020 ; Wang X. et al, 2020 ; Xu et al, 2020 ; Zhu et al, 2020 ; see Table 3 for examples of ligand targeting in glioma research).…”

“…Here, the delivered gene includes a tumor-specific promoter (highly functional only in cancer cells), which will secure a well-localized expression of the transgene, limited to occur only inside the cancer cells of interest. Posttranscriptional regulations of the product encoded by the exogenously delivered gene are achieved by controlling RNA splicing, RNA stability, and initiation of the RNA translation once it is present in the cancer cell ( Maier-Hauff et al, 2007 ; Kim et al, 2010 ; Wegscheid et al, 2014 ; Cheng Y. et al, 2016 ; Shen et al, 2017 ; Yu et al, 2017 ; Hua et al, 2018 ; Daniel et al, 2019 ; Denora et al, 2019 ; Dufort et al, 2019 ; Kunoh et al, 2019 ; Luque-Michel et al, 2019 ; Ruan et al, 2019 ; Rego et al, 2019 , 2020 ; Shi et al, 2019 ; Sousa et al, 2019 ; Ye et al, 2019 ; Zhang et al, 2019 ; Zhao et al, 2019 ; ZhuGe et al, 2019 ; Alves et al, 2020 ; Caban-Toktas et al, 2020 ; Chung et al, 2020 ; Ferreira et al, 2020 ; Kazmi et al, 2020 ; Liang et al, 2020 ; Martinez-Rovira et al, 2020 ; Meng et al, 2020 ; Roberts et al, 2020 ; Ullah et al, 2020 ; Wang H. et al, 2020 ; Wang X. et al, 2020 ; Xu et al, 2020 ; Zhu et al, 2020 ).…”

Nanoparticle-Based Radiosensitization

“…With successful delivery of nanoparticle radiosensitizers, there is translatable scope for improving the therapeutic outcomes in treating cancer, especially where radiotherapy is limited by sparing healthy tissues in radioresistant cancers. This is exemplified, for example, in the work of Dr (MD) Kazmi et al [4], who report on the sensitization effects of gold nanoparticles in the problematic indication of glioblastoma.…”