Determining the Radiation Enhancement Effects of Gold Nanoparticles in Cells in a Combined Treatment with Cisplatin and Radiation at Therapeutic Megavoltage Energies.

Published on May 22, 2018in Cancers6.126
· DOI :10.3390/CANCERS10050150
Celina Yang8
Estimated H-index: 8
(RyeU: Ryerson University),
Kyle Bromma7
Estimated H-index: 7
(UVic: University of Victoria)
+ 2 AuthorsDevika B. Chithrani17
Estimated H-index: 17
(RyeU: Ryerson University)
Combined use of chemotherapy and radiation therapy is commonly used in cancer treatment, but the toxic effects on normal tissue are a major limitation. This study assesses the potential to improve radiation therapy when combining gold nanoparticle (GNP) mediated radiation sensitization with chemoradiation compared to chemoradiation alone. Incorporation of GNPs with 2 Gy, 6 MV (megavoltage) radiation resulted in a 19 ± 6% decrease in survival of MDA-MB-231 cells. Monte-Carlo simulations were performed to assess dosimetric differences in the presence of GNPs in radiation. The results show that physics dosimetry represents a small fraction of the observed effect. The survival fraction of the cells exposed to GNPs, cisplatin, and radiation was 0.16 ± 0.007, while cells treated with cisplatin and radiation only was 0.23 ± 0.011. The presence of GNPs resulted in a 30 ± 6% decrease in the survival, having an additive effect. The concentration of the GNPs and free drug used for this study was 0.3 and 435 nM, respectively. These concentrations are relatively lower and achievable in an in vivo setting. Hence, the results of our study would accelerate the incorporation of GNP-mediated chemoradiation into current cancer therapeutic protocols in the near future.
Figures & Tables
📖 Papers frequently viewed together
6 Citations
7 Citations
#1Celina Yang (RyeU: Ryerson University)H-Index: 8
#2Kyle Bromma (UVic: University of Victoria)H-Index: 7
Last. Devika B. Chithrani (RyeU: Ryerson University)H-Index: 17
view all 3 authors...
Optimizing the interface between nanoparticles (NPs) and the biological environment at various levels should be considered for improving delivery of NPs to the target tumor area. For NPs to be successfully delivered to cancer cells, NPs needs to be functionalized for circulation through the blood vessels. In this study, accumulation of Polyethylene Glycol (PEG) functionalized gold nanoparticles (GNPs) was first tested using in vitro monolayer cells and multilayer cell models prior to in vivo mod...
15 CitationsSource
#1Mengmeng Liu (CAS: Chinese Academy of Sciences)H-Index: 4
#1Mengmeng Liu (CAS: Chinese Academy of Sciences)H-Index: 20
Last. Chunhai Fan (CAS: Chinese Academy of Sciences)H-Index: 116
view all 14 authors...
The interaction of nanoparticles intracellularly has been investigated widely but the mechanisms of such interactions are not fully understood. Here, the authors utilize a semi-quantitative technique to assess the intracellular transportation and clustering potential of nanoparticles in real-time.
75 CitationsSource
#1Wonmo Sung (Harvard University)H-Index: 11
#2Sung-Joon Ye (SNU: Seoul National University)H-Index: 6
Last. Jan Schuemann (Harvard University)H-Index: 23
view all 9 authors...
The radiosensitization effect of gold nanoparticles (GNPs) has been demonstrated both in vitro and in vivo in radiation therapy. The purpose of this study was to systematically assess the biological effectiveness of GNPs distributed in the extracellular media for realistic cell geometries. TOPAS-nBio simulations were used to determine the nanometre-scale radial dose distributions around the GNPs, which were subsequently used to predict the radiation dose response of cells surrounded by GNPs. MDA...
35 CitationsSource
#1Lei CuiH-Index: 5
#2Sohyoung HerH-Index: 7
Last. Christine Allen (U of T: University of Toronto)H-Index: 57
view all 8 authors...
Gold nanoparticles (AuNPs) and cisplatin have been explored in concomitant chemoradiotherapy, wherein they elicit their effects by distinct and overlapping mechanisms. Cisplatin is one of the most frequently utilized radiosensitizers in the clinical setting; however, the therapeutic window of cisplatin-aided chemoradiotherapy is limited by its toxicity. The goal of this study was to determine whether AuNPs contribute to improving the treatment response when combined with fractionated cisplatin-b...
25 CitationsSource
#1Aimee L. McNamara (Harvard University)H-Index: 16
#2Changran Geng (Harvard University)H-Index: 9
Last. Jan Schuemann (Harvard University)H-Index: 23
view all 9 authors...
Abstract Computational simulations offer a powerful tool for quantitatively investigating radiation interactions with biological tissue and can help bridge the gap between physics, chemistry and biology. The TOPAS collaboration is tackling this challenge by extending the current Monte Carlo tool to allow for sub-cellular in silico simulations in a new extension, TOPAS-nBio. TOPAS wraps and extends the Geant4 Monte Carlo simulation toolkit and the new extension allows the modeling of particles do...
45 CitationsSource
#1Kaspar Haume (OU: Open University)H-Index: 3
#2Soraia Rosa ('QUB': Queen's University Belfast)H-Index: 3
Last. Nigel J. Mason (OU: Open University)H-Index: 40
view all 9 authors...
Radiotherapy is currently used in around 50% of cancer treatments and relies on the deposition of energy directly into tumour tissue. Although it is generally effective, some of the deposited energy can adversely affect healthy tissue outside the tumour volume, especially in the case of photon radiation (gamma and X-rays). Improved radiotherapy outcomes can be achieved by employing ion beams due to the characteristic energy deposition curve which culminates in a localised, high radiation dose (i...
173 CitationsSource
#1Raja Modhugoor Devendiran (CLRI: Central Leather Research Institute)H-Index: 3
#2Senthil kumar Chinnaiyan (Anna University)H-Index: 3
Last. Uma Tirichurapalli Sivagnanam (CLRI: Central Leather Research Institute)H-Index: 10
view all 7 authors...
In the present work, gold nanoparticles (GNPs) were successfully prepared by green synthesis using a strong antioxidant Quercetin (Q) as a reducing agent in the presence of Dextran Sulphate (DS) as a stabilizing agent at room temperature (DS–Q–GNPs). DS–Q–GNPs were characterized by several in vitro techniques to understand their physiochemical and biological properties. However, the average particle size was found to be around 38 nm, and the zeta potential of DS–Q–GNPs was found to be around −42...
9 CitationsSource
#1Cuihong Wang (SDU: Shandong University)H-Index: 4
#2Yuhua Jiang (SDU: Shandong University)H-Index: 8
Last. Likuan Hu (SDU: Shandong University)H-Index: 7
view all 4 authors...
Background Gold nanoparticles (GNPs) have been conceived to cause increased cytotoxicity of radiotherapy in human malignant cells. Greater uptake of GNPs by cells may induce increased radiation effects. Here we report the radiosensitization effect of glucose-capped GNPs (Glu-GNPs) with different sizes (16 nm and 49 nm) on MDA-MB-231 cells in the presence of megavoltage X-rays.
38 CitationsSource
#1Tatiana Wolfe (University of Texas MD Anderson Cancer Center)H-Index: 4
#2Dev K. Chatterjee (University of Texas MD Anderson Cancer Center)H-Index: 11
Last. Sunil Krishnan (University of Texas MD Anderson Cancer Center)H-Index: 79
view all 9 authors...
We report potent radiosensitization of prostate cancers in vitro and in vivo using goserelin-conjugated gold nanorods. Progressive receptor-mediated internalization of conjugated nanorods over time increases the radiation interaction cross-section of cells and contributes to the effects observed in vitro. The low concentrations of gold required, the long interval between injection of nanoparticles and radiation, and the use of megavoltage radiation to generate radiosensitization in vivo foretell...
97 CitationsSource
#1Yuting Lin (Harvard University)H-Index: 7
#2Stephen J. McMahon ('QUB': Queen's University Belfast)H-Index: 31
Last. Jan Schuemann (Harvard University)H-Index: 23
view all 4 authors...
Gold nanoparticles (GNPs) have shown potential as a radiosensitizer for radiation therapy using photon beams. Recently, experimental studies have been carried out using proton beams showing the GNP enhanced responses in proton therapy. In this work, we established a biological model to investigate the change in survival of irradiated cells due to the radiosensitizing effect of gold nanoparticles. Results for proton, megavoltage (MV) photon and kilovoltage (kV) photon beams are compared. For each...
75 CitationsSource
Cited By15
About half of cancer patients (50%) receive radiotherapy (RT) for the treatment of local tumors. However, one of the main obstacles in RT is the close proximity of adjacent organs at risk, resulting in treatment doses being limited by significant tissue toxicity, hence preventing the necessary dose escalation that would guarantee local control. Effective local cancer therapy is needed to avoid progression of tumors and to decrease the development of systemic metastases which may further increase...
#1Chih-Sheng Chiang (PRC: China Medical University (PRC))H-Index: 10
Last. Tse-Ying LiuH-Index: 5
view all 8 authors...
Although boron neuron capture therapy (BNCT) has enabled the delivery of stronger radiation dose to glioblastoma multiforme (GBM) cells for precision radiotherapy (RT), patients in need are almost unable to access the treatment due to insufficient operating devices. Therefore, we developed targeted sensitization-enhanced radiotherapy (TSER), a strategy that could achieve precision cell-targeted RT using common linear accelerators. TSER, which involves the combination of GoldenDisk (GD; a spheric...
Purpose This study aimed to quantify synergetic effects induced by bismuth oxide nanoparticles (BiONPs), cisplatin (Cis) and baicalein-rich fraction (BRF) natural-based agent on the reactive oxygen species (ROS) generation and radiosensitization effects under irradiation of clinical radiotherapy beams of photon, electron and HDR-brachytherapy. The combined therapeutic responses of each compound and clinical radiotherapy beam were evaluated on breast cancer and normal fibroblast cell line. Method...
#1Arvind Pandey (Houston Methodist Hospital)H-Index: 24
#1Arvind PandeyH-Index: 9
Last. Carly S. FilgueiraH-Index: 11
view all 9 authors...
It has been suggested that particle size plays an important role in determining the genotoxicity of gold nanoparticles (GNPs). The purpose of this study was to compare the potential radio-sensitization effects of two different sized GNPs (3.9 and 37.4 nm) fabricated and examined in vitro in Lewis lung carcinoma (LLC) as a model of non-small cell lung cancer through use of comet and clonogenic assays. After treatment with 2Gy X-ray irradiation, both particle sizes demonstrated increased DNA damag...
62 CitationsSource
According to the global cancer observatory (GLOBOCAN), there are approximately 18 million new cancer cases per year worldwide. Cancer therapies are largely limited to surgery, radiotherapy, and chemotherapy. In radiotherapy and chemotherapy, the maximum tolerated dose is presently being used to treat cancer patients. The integrated development of innovative nanoparticle (NP) based approaches will be a key to address one of the main issues in both radiotherapy and chemotherapy: normal tissue toxi...
5 CitationsSource
#1Gabriel Charest (Université de Sherbrooke)H-Index: 8
#2Thititip Tippayamontri (Université de Sherbrooke)H-Index: 5
Last. Léon Sanche (Université de Sherbrooke)H-Index: 75
view all 7 authors...
A liposomal formulation of gold nanoparticles (GNPs) and carboplatin, named LipoGold, was produced with the staggered herringbone microfluidic method. The radiosensitizing potential of LipoGold and similar concentrations of non-liposomal GNPs, carboplatin and oxaliplatin was evaluated in vitro with the human colorectal cancer cell line HCT116 in a clonogenic assay. Progression of HCT116 tumor implanted subcutaneously in NU/NU mice was monitored after an irradiation of 10 Gy combined with either ...
2 CitationsSource
#1Aaron Bannister (UVic: University of Victoria)H-Index: 3
#2Kyle Bromma (UVic: University of Victoria)H-Index: 7
Last. Devika B. ChithraniH-Index: 17
view all 9 authors...
Objective:One of the major issues in current radiotherapy (RT) is the normal tissue toxicity. A smart combination of agents within the tumor would allow lowering the RT dose required while minimizi...
8 CitationsSource
#1Francisco Silva (IST: Instituto Superior Técnico)H-Index: 8
#2António Paulo (IST: Instituto Superior Técnico)H-Index: 27
Last. Maria Paula Cabral Campello (IST: Instituto Superior Técnico)H-Index: 13
view all 14 authors...
Gold nanoparticles (AuNPs) are interesting for the design of new cancer theranostic tools, mainly due to their biocompatibility, easy molecular vectorization, and good biological half-life. Herein, we report a gold nanoparticle platform as a bimodal imaging probe, capable of coordinating Gd3+ for Magnetic Resonance Imaging (MRI) and 67Ga3+ for Single Photon Emission Computed Tomography (SPECT) imaging. Our AuNPs carry a bombesin analogue with affinity towards the gastrin releasing peptide recept...
5 CitationsSource
#1Noor Nabilah Talik Sisin (RMIT: RMIT University)H-Index: 3
#2Khairunisak Abdul Razak (Universiti Sains Malaysia)H-Index: 21
Last. Wan Nordiana RahmanH-Index: 9
view all 11 authors...
Purpose: The aim of this study was to investigate the potential of the synergetic triple therapeutic combination encompassing bismuth oxide nanoparticles (BiONPs), cisplatin (Cis), and high dose rate (HDR) brachytherapy with Ir-192 source in breast cancer and normal fibroblast cell line. Methods: In vitro models of breast cancer cell lines (MCF-7, MDA-MB-231) and normal fibroblast cell line (NIH/3T3) were employed. Cellular localization and cytotoxicity studies were conducted prior to inspection...
3 CitationsSource
#1Keywan MortezaeeH-Index: 26
#2Masoud Najafi (Kermanshah University of Medical Sciences)H-Index: 33
Last. Amirhossein Ahmadi (Mazandaran University of Medical Sciences)H-Index: 26
view all 6 authors...
Abstract Nanotechnology is a growing science that may provide several new applications for medicine, food preservation, diagnostic technologies, and sanitation. Despite its beneficial applications, there are several questions related to the safety of nanomaterials for human use. The development of nanotechnology is associated with some concerns because of the increased risk of carcinogenesis following exposure to nanomaterials. The increased levels of reactive oxygen species (ROS) that are due t...
42 CitationsSource