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

2019 ◽  
Author(s):  
Farasat Kazmi ◽  
Kate A. Vallis ◽  
Balamurugan A. Vellayappan ◽  
Aishwarya Bandla ◽  
Duan Yukun ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Cancer Cell Line ◽  
Radiation Sensitivity ◽  
Dark Field ◽  
Metal Nanoparticle ◽  
X Rays ◽  
Survival Fraction ◽  
Significant Difference ◽  
Vitro Model

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.

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

2020 ◽  
Vol 21 (2) ◽  
pp. 429 ◽  
Author(s):  
Farasat Kazmi ◽  
Katherine A. Vallis ◽  
Balamurugan A. Vellayappan ◽  
Aishwarya Bandla ◽  
Duan Yukun ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Cancer Cell Line ◽  
Radiation Sensitivity ◽  
Dark Field ◽  
Metal Nanoparticle ◽  
X Rays ◽  
Survival Fraction ◽  
Significant Difference ◽  
Vitro Model

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.

scholarly journals Combined cancer therapy using gold nanoparticles

2021 ◽  
Author(s):  
Celina Yang
Keyword(s):  
Gold Nanoparticles ◽  
Radiation Therapy ◽  
Peptide Sequence ◽  
X Rays ◽  
Combined Chemotherapy ◽  
Survival Fraction ◽  
Rgd Peptides ◽  
Efficient Delivery ◽  
Significant Toxicity ◽  
Significant Difference

This dissertation presents the effect of peptide-modified 10 nm gold nanoparticles (GNPs) with chemotherapeutic drugs, bleomycin and cisplatin, and 2 Gy of 6 MV X-ray irradiation in MDA-MB-231 cells. The GNPs were modified with a peptide sequence containing an ‘RGD’ amino acid motif. Bleomycin binds to the surface of the GNPs through a thiol bond and cisplatin has no known significant interaction with the GNP surface. No significant toxicity was induced by introducing GNPs to MDA-MB-231 cells at the 0.3 nM concentration used throughout this dissertation. The surface modification with ‘RGD’ peptides increased accumulation of the GNP constructs 6~7 fold compared to the unmodified counterparts. There was no significant difference in the accumulation of GNPs in the presence of bleomycin or cisplatin. These results suggest that the presence of chemotherapeutics do not affect the accumulation of peptide modified GNPs into cells. The effect of having GNPs with chemotherapeutics was examined. The presence of GNPs with bleomycin decreased the survival of MDA-MB-231 cells by 18 ± 3 % compared to treatment with the same concentration of free bleomycin. Treating cells with GNPs and cisplatin did not have a significant difference in survival compared to the same concentration of free cisplatin treatment. This suggests that conjugating chemotherapeutics onto the GNPs can result in a more efficient delivery of the drug. If the drug does not bind to the GNP surface, having GNPs in the media does not interfere with the uptake of the drug. The effect of radiosensitization in the presence of GNPs was studied by incubating cells with 0.3 nM GNPs prior to irradiation with 2 Gy of 6 MV X-rays. The survival fraction decreased by 19 ± 6 % compared to the irradiated control condition. Lastly, the triple combined effect of GNPs, chemotherapeutics, and irradiation was investigated. The presence of GNPs had an advantage to the combined chemotherapy and radiation therapy. Based on results from these studies, GNPs can be used in addition to combined chemotherapy and radiation therapy for improved outcomes in cancer treatment

scholarly journals Combined cancer therapy using gold nanoparticles

2021 ◽  
Author(s):  
Celina Yang
Keyword(s):  
Gold Nanoparticles ◽  
Radiation Therapy ◽  
Peptide Sequence ◽  
X Rays ◽  
Combined Chemotherapy ◽  
Survival Fraction ◽  
Rgd Peptides ◽  
Efficient Delivery ◽  
Significant Toxicity ◽  
Significant Difference

This dissertation presents the effect of peptide-modified 10 nm gold nanoparticles (GNPs) with chemotherapeutic drugs, bleomycin and cisplatin, and 2 Gy of 6 MV X-ray irradiation in MDA-MB-231 cells. The GNPs were modified with a peptide sequence containing an ‘RGD’ amino acid motif. Bleomycin binds to the surface of the GNPs through a thiol bond and cisplatin has no known significant interaction with the GNP surface. No significant toxicity was induced by introducing GNPs to MDA-MB-231 cells at the 0.3 nM concentration used throughout this dissertation. The surface modification with ‘RGD’ peptides increased accumulation of the GNP constructs 6~7 fold compared to the unmodified counterparts. There was no significant difference in the accumulation of GNPs in the presence of bleomycin or cisplatin. These results suggest that the presence of chemotherapeutics do not affect the accumulation of peptide modified GNPs into cells. The effect of having GNPs with chemotherapeutics was examined. The presence of GNPs with bleomycin decreased the survival of MDA-MB-231 cells by 18 ± 3 % compared to treatment with the same concentration of free bleomycin. Treating cells with GNPs and cisplatin did not have a significant difference in survival compared to the same concentration of free cisplatin treatment. This suggests that conjugating chemotherapeutics onto the GNPs can result in a more efficient delivery of the drug. If the drug does not bind to the GNP surface, having GNPs in the media does not interfere with the uptake of the drug. The effect of radiosensitization in the presence of GNPs was studied by incubating cells with 0.3 nM GNPs prior to irradiation with 2 Gy of 6 MV X-rays. The survival fraction decreased by 19 ± 6 % compared to the irradiated control condition. Lastly, the triple combined effect of GNPs, chemotherapeutics, and irradiation was investigated. The presence of GNPs had an advantage to the combined chemotherapy and radiation therapy. Based on results from these studies, GNPs can be used in addition to combined chemotherapy and radiation therapy for improved outcomes in cancer treatment

scholarly journals Radiosensitization of Prostate Cancers In Vitro and In Vivo to Erbium-filtered Orthovoltage X-rays Using Actively Targeted Gold Nanoparticles

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Allison M. Khoo ◽  
Sang Hyun Cho ◽  
Francisco J. Reynoso ◽  
Maureen Aliru ◽  
Kathryn Aziz ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
X Rays ◽  
Prostate Cancers

scholarly journals Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1676
Author(s):  
Giulia Rossi ◽  
Martina Placidi ◽  
Chiara Castellini ◽  
Francesco Rea ◽  
Settimio D'Andrea ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Cellular Damage ◽  
X Rays ◽  
Adolescent Cancer ◽  
Radiation Induced ◽  
Vitro Model ◽  
Underlying Mechanisms

Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 μM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period.

Performance changes of venous valves following tissue treatment with novel in vitro system

2018 ◽  
Vol 34 (5) ◽  
pp. 347-354
Author(s):  
Garrett Easson ◽  
Megan Laughlin ◽  
Hanna Jensen ◽  
Kevin Haney ◽  
Marc Girardot ◽  
...  
Keyword(s):  
High Speed ◽  
In Vitro Model ◽  
Closing Time ◽  
Venous Valve ◽  
Orifice Area ◽  
Treatment Methods ◽  
Venous Valves ◽  
Significant Difference ◽  
Vitro Model

Objectives The purpose of this study is to test venous valve performance and identify differences between native tissue and replacement devices developed with traditional tissue treatment methods using a new in vitro model with synchronized hemodynamic parameters and high-speed valve image acquisition. Methods An in vitro model mimicking the venous circulation to test valve performance was developed using hydrostatic pressure driven flow. Fresh and glutaraldehyde-treated vein segments were placed in the setup and opening/closing of the valves was captured by a high-speed camera. Hemodynamic data were obtained using synchronized hardware and virtual instrumentation. Results Geometric orifice area and opening/closing time of the valves was evaluated at the same hemodynamic conditions. A reduction in geometric orifice area of 27.2  ± 14.8% (p < 0.05) was observed following glutaraldehyde fixation. No significant difference in opening/closing time following chemical fixation was observed. Conclusions The developed in vitro model was shown to be an effective method for measuring the performance of venous valves. The observed decrease in geometric orifice area following glutaraldehyde treatment indicates a decrease in flow through the valve, demonstrating the consequences of traditional tissue treatment methods.

scholarly journals Trastuzumab-Modified Gold Nanoparticles Labeled with 211At as a Prospective Tool for Local Treatment of HER2-Positive Breast Cancer

Nanomaterials ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 632 ◽  
Author(s):  
Łucja Dziawer ◽  
Agnieszka Majkowska-Pilip ◽  
Damian Gaweł ◽  
Marlena Godlewska ◽  
Marek Pruszyński ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gold Nanoparticles ◽  
Local Treatment ◽  
Growth Factor Receptor ◽  
Dark Field ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Biological Studies ◽  
Positive Breast Cancer

Highly localized radiotherapy with radionuclides is a commonly used treatment modality for patients with unresectable solid tumors. Herein, we propose a novel α-nanobrachytherapy approach for selective therapy of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This uses local intratumoral injection of 5-nm-diameter gold nanoparticles (AuNPs) labeled with an α-emitter (211At), modified with polyethylene glycol (PEG) chains and attached to HER2-specific monoclonal antibody (trastuzumab). The size, shape, morphology, and zeta potential of the 5 nm synthesized AuNPs were characterized by TEM (Transmission Electron Microscopy) and DLS (Dynamic Light Scattering) techniques. The gold nanoparticle surface was modified by PEG and subsequently used for antibody immobilization. Utilizing the high affinity of gold for heavy halogens, the bioconjugate was labelled with 211At obtained by α irradiation of the bismuth target. The labeling yield of 211At was greater than 99%. 211At bioconjugates were stable in human serum. Additionally, in vitro biological studies indicated that 211At-AuNP-PEG-trastuzumab exhibited higher affinity and cytotoxicity towards the HER2-overexpressing human ovarian SKOV-3 cell line than unmodified nanoparticles. Confocal and dark field microscopy studies revealed that 211At-AuNP-PEG-trastuzumab was effectively internalized and deposited near the nucleus. These findings show promising potential for the 211At-AuNP-PEG-trastuzumab radiobioconjugate as a perspective therapeutic agent in the treatment of unresectable solid cancers expressing HER2 receptors.

160 Exposure to Cadmium Affects Oocyte and Embryo Competence in Cattle

2018 ◽  
Vol 30 (1) ◽  
pp. 219
Author(s):  
C. De Canditiis ◽  
N. Pagano ◽  
V. Franco ◽  
I. Paradiso ◽  
É. C. Dos Santos ◽  
...  
Keyword(s):  
Embryo Development ◽  
Cumulus Cells ◽  
Early Embryo ◽  
Dapi Staining ◽  
Vitro Fertilization ◽  
Nuclear Maturation ◽  
Significant Difference ◽  
Vitro Model ◽  
Hoechst Staining

There is a growing worldwide concern regarding the increased release of the heavy metal cadmium (Cd) in the environment, due to several industrial processes, as it is known to affect health. Among other heavy metals, Cd is widely recognised to influence the reproductive system at different levels, interfering with both gametes and embryo functions in several species (Thompson and Bannigan, 2008 Reprod. Toxicol. 25, 304-315). The in vitro model can be used to mimic environmental conditions allowing us to evaluate their effect on oocyte maturation and early embryo development. Therefore, the aim of this study was to evaluate the influence of different Cd concentrations on nuclear maturation, apoptosis in cumulus cells, and cleavage and blastocyst yields in cattle. For this purpose, abattoir-derived bovine oocytes were in vitro matured, fertilized, and cultured according to standard procedures (Rubessa et al. 2011 Theriogenology 76, 1347-1355). In particular, oocytes were matured with 0 (control; n = 126), 0.1 μM (n = 139), 1 μM (n = 134), and 10 μM of Cd (n = 135), at 39°C under humidified air with 5% CO2, 7% O2, and 88% N2. For each replicate, after 22 h of maturation, a representative sample of oocytes (n = 10 per each group) was used to evaluate nuclear maturation by 4′,6-diamidino-2-phenylindole (DAPI) staining and another sample (n = 10 per each group) to assess cumulus-cells complex apoptosis by TUNEL/Hoechst staining (Pocar et al. 2005 Reproduction 130, 857-868). The remaining oocytes were in vitro fertilized and cultured with 0 (n = 106), 0.1 μM (n = 119), 1 μM (n = 114), and 10 μM (n = 115) Cd. The experiment was repeated 3 times. On Day 8 post-IVF, the blastocyst yields were recorded. Differences among groups were analysed by ANOVA, with the least significant difference method used as a post hoc test. Data are presented as means ± SE. Unexpectedly, the exposure of oocytes to Cd during IVM did not affect the percentage of oocytes undergoing nuclear maturation (on average 96.3 ± 2.3). In contrast, concentrations of 1 and 10 μM Cd increased the percentage of apoptotic cumulus-cells in cumulus–oocyte complexes (COC) compared with the control (3.4 ± 0.4, 10.6 ± 1.8, 15.0 ± 0.9, 16.7 ± 4.0, respectively, with 0, 0.1, 1, and 10 μM; P < 0.05). It is worth pointing out that with the highest concentration, cumulus expansion did not occur and cumulus cells appeared detached from the oocyte. Likewise, 1 and 10 μM Cd decreased cleavage rates compared with the control (68.7 ± 1.8, 54.3 ± 5.0, 58.5 ± 4.2 and 2.8 ± 2.6, respectively, with 0, 0.1, 1, and 10 μM Cd; P < 0.01). Finally, blastocyst yields decreased when oocytes were treated with 0.1 μM Cd and no development to blastocyst was observed at the 2 higher concentrations (35.1 ± 1.7, 26.2 ± 3.1, 0, 0, respectively, with 0, 0.1, 1, and 10 μM; P < 0.01). In conclusion, exposure to Cd during maturation negatively affects bovine COC, as indicated by the increased apoptotic index in cumulus cells, without influencing the nuclear maturation process. Furthermore, the presence of Cd during in vitro fertilization and culture severely impairs both the fertilization and post-fertilization embryo development.

T-614 inhibits human aortic adventitial fibroblast proliferation and promotes interleukin-8 production in vitro

Vascular ◽  
2019 ◽  
Vol 28 (3) ◽  
pp. 314-320
Author(s):  
Weiping Ci ◽  
Tian Wang ◽  
Taotao Li ◽  
Jin Wan
Keyword(s):  
Cell Viability ◽  
Vascular Wall ◽  
Underlying Mechanism ◽  
Interleukin 8 ◽  
Control Group ◽  
Survival Fraction ◽  
Tnf Α ◽  
Significant Difference ◽  
Factor Α

Objectives The effect and underlying mechanism of T-614 (iguratimod) on Takayasu’s arteritis (TA) are unknown. Here, we report the effects of T-614 on cell proliferation and interleukin-8 (IL-8) production in human aortic adventitial fibroblasts (HAAFs) in vitro and explore its initial benefit in terms of vascular wall inflammation and remodeling for patients with TA. Methods HAAFs were cultured with 0, 5, 50, 100, or 250 μg/ml T-614 in the absence or presence of tumor necrosis factor-α (TNF-α) in vitro. Cell viability was determined by a modified MTT assay. Supernatant IL-8 levels were measured by enzyme-linked immunosorbent assays. Results In the presence of TNF-α, compared to that in the control group, cell viability of HAAFs significantly decreased in the 50, 100, and 250 μg/ml T-614 treatment groups (OD value: P <  0.01, P <  0.001, P <  0.001, respectively; survival fraction (SF): P <  0.05, P <  0.001, P <  0.001, respectively). However, there was no significant difference in cell viability between TNF-α-stimulated and unstimulated groups at the same concentration of T-614. In the absence or presence of TNF-α, T-614 suppressed HAAF cell viability dose-dependently (OD value: r = −0.915, P =  0.000; r = −0.926, P =  0.000, respectively; SF: r = −0.897, P =  0.000; r = −0.885, P =  0.000, respectively). Compared to that in the control group, in the absence of TNF-α, IL-8 levels in the 5 and 100 μg/ml T-614-treated groups were significantly higher ( P <  0.05); in the presence of TNF-α, IL-8 levels in the 5, 50, and 100 μg/ml T-614-treated groups were significantly higher ( P <  0.001, P <  0.001, P <  0.01, respectively). Further, there was a negative correlation between supernatant IL-8 levels and T-614 concentration in groups stimulated with TNF-α ( r = −0.670, P =  0.000), but there was no significant correlation between these parameters in groups that were not stimulated with TNF-α. Conclusions In the absence or presence of TNF-α, T-614 can inhibit HAAF proliferation and promote IL-8 production in vitro; therefore, it could be used to prevent adventitial thickening of the aorta and improve vascular remodeling in inflammatory environments in vitro and might provide a new immunotherapeutic intervention for TA.

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