scholarly journals Combined cancer therapy using gold nanoparticles

2021 ◽  
Author(s):  
Celina Yang

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

2021 ◽  
Author(s):  
Celina Yang

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


Author(s):  
Farasat Kazmi ◽  
Kate A. Vallis ◽  
Balamurugan A. Vellayappan ◽  
Aishwarya Bandla ◽  
Duan Yukun ◽  
...  

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.


2020 ◽  
Vol 21 (2) ◽  
pp. 429 ◽  
Author(s):  
Farasat Kazmi ◽  
Katherine A. Vallis ◽  
Balamurugan A. Vellayappan ◽  
Aishwarya Bandla ◽  
Duan Yukun ◽  
...  

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.


2021 ◽  
Author(s):  
Mathew John Rajic

Gold nanoparticles have long been considered for use in conjunction with radiation therapy to enhance dose in a local tumor regions. However, limitation in cellular accumulation remains a hindrance for treatments to extend to clinical levels. Ultrasound and microbubbles have been shown to enhance the delivery of chemotherapies, genetic material and other molecules. This goal of this study was to demonstrate, for the first time to the best of our knowledge, the increase in PEGylated gold nanoparticle accumulation in cells due to the addition of ultrasound and microbubbles, and survival fraction. The results display approximate 3 fold increase in intracellular gold content independent of nanoparticle size, resulting in a 5 fold increase in cell death. Additionally, it was shown that USMB can facilitate nuclear localization of gold nanoparticles with nuclear localized signals to further enhance radiation therapy.


2021 ◽  
Author(s):  
Mathew John Rajic

Gold nanoparticles have long been considered for use in conjunction with radiation therapy to enhance dose in a local tumor regions. However, limitation in cellular accumulation remains a hindrance for treatments to extend to clinical levels. Ultrasound and microbubbles have been shown to enhance the delivery of chemotherapies, genetic material and other molecules. This goal of this study was to demonstrate, for the first time to the best of our knowledge, the increase in PEGylated gold nanoparticle accumulation in cells due to the addition of ultrasound and microbubbles, and survival fraction. The results display approximate 3 fold increase in intracellular gold content independent of nanoparticle size, resulting in a 5 fold increase in cell death. Additionally, it was shown that USMB can facilitate nuclear localization of gold nanoparticles with nuclear localized signals to further enhance radiation therapy.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Allison M. Khoo ◽  
Sang Hyun Cho ◽  
Francisco J. Reynoso ◽  
Maureen Aliru ◽  
Kathryn Aziz ◽  
...  

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 923.3-923
Author(s):  
S. Boussaid ◽  
M. Mrabet ◽  
S. Jemmali ◽  
H. Sahli ◽  
H. Ajlani ◽  
...  

Background:Tuberculosis (TB) is no longer a disease limited to developing nations and is still a major cause of significant morbidity and mortality worldwide. It can affect the different parts of the spine.Objectives:The aim of this study was to determine the preferred spinal location of TB.Methods:We conduct a retrospective and descriptive study in a single rheumatology department. Data were collected from observations of patients hospitalized in the past 20 years (2000-2020) who have been diagnosed with tuberculous spondylodiscitis (TS).Results:Fifty-two patients were included (37F/15M). Their mean age was 55.21 years ± 17.79 [19-91]. TS was more frequently unifocal (75%) than multifocal (25%). Lumbar spine involvement was the most common (57.7%) and more frequent in women (63.3%) but with no statistically significant difference (p = 0.2). Other localizations were described such as: dorso-lumbar (21.2%), dorsal (15.4%), lumbosacral (3.8%) and cervical (1.9%). Lumbar pain was present in 34 patients (65.4%) and 29 patients (55.8%) suffered from segmental lumbar stiffness. Imaging was contributive by showing the vertebral location using standard X-rays, computed tomography and magnetic resonance imaging. Disc pinch, erosion of vertebral plateaus and vertebral collapse were the major signs (82.7%, 65.4% and 67.3%, respectively).Conclusion:TS is a rare but serious clinical condition which may lead to severe deformity and early or late neurological complications. Spinal involvement is often unifocal and mostly diagnosed with lumbar pain or stiffness. Multifocal forms, touching several parts of the spine, however remain rare. Our findings remain consistent with those of the literature.Disclosure of Interests:None declared


2021 ◽  
Vol 22 (3) ◽  
pp. 1418
Author(s):  
Elham Shahhoseini ◽  
Masao Nakayama ◽  
Terrence J. Piva ◽  
Moshi Geso

This study examined the effects of gold nanoparticles (AuNPs) and/or ionizing radiation (IR) on the viability and motility of human primary colon epithelial (CCD841) and colorectal adenocarcinoma (SW48) cells as well as human primary epidermal melanocytes (HEM) and melanoma (MM418-C1) cells. AuNPs up to 4 mM had no effect on the viability of these cell lines. The viability of the cancer cells was ~60% following exposure to 5 Gy. Exposure to 5 Gy X-rays or 1 mM AuNPs showed the migration of the cancer cells ~85% that of untreated controls, while co-treatment with AuNPs and IR decreased migration to ~60%. In the non-cancerous cell lines gap closure was enhanced by ~15% following 1 mM AuNPs or 5 Gy treatment, while for co-treatment it was ~22% greater than that for the untreated controls. AuNPs had no effect on cell re-adhesion, while IR enhanced only the re-adhesion of the cancer cell lines but not their non-cancerous counterparts. The addition of AuNPs did not enhance cell adherence. This different reaction to AuNPs and IR in the cancer and normal cells can be attributed to radiation-induced adhesiveness and metabolic differences between tumour cells and their non-cancerous counterparts.


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