Gold nanoparticle mediated combined cancer therapy

Abstract Background The combined use of radiation therapy and chemotherapy is commonly being used in cancer treatment. The side effects of the treatment can be further minimized through targeted delivery of anticancer drugs and local enhancement of the radiation dose. Gold nanoparticles (GNPs) can p...

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Main Authors: Celina Yang, Kyle Bromma, Caterina Di Ciano-Oliveira, Gaetano Zafarana, Monique van Prooijen, Devika B. Chithrani
Format: Article
Language:English
Published: BMC 2018-05-01
Series:Cancer Nanotechnology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12645-018-0039-3
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author Celina Yang
Kyle Bromma
Caterina Di Ciano-Oliveira
Gaetano Zafarana
Monique van Prooijen
Devika B. Chithrani
author_facet Celina Yang
Kyle Bromma
Caterina Di Ciano-Oliveira
Gaetano Zafarana
Monique van Prooijen
Devika B. Chithrani
author_sort Celina Yang
collection DOAJ
description Abstract Background The combined use of radiation therapy and chemotherapy is commonly being used in cancer treatment. The side effects of the treatment can be further minimized through targeted delivery of anticancer drugs and local enhancement of the radiation dose. Gold nanoparticles (GNPs) can play a significant role in this regard since GNPs can be used as radiation dose enhancers and anticancer drug carriers. Anticancer drug, bleomycin, was chosen as the model drug, since it could be easily conjugated onto GNPs through the gold–thiol bond. Methods Gold nanoparticles of size 10 nm were synthesized using the citrate reduction method. The surface of The GNPs was modified with a peptide sequence (CKKKKKKGGRGDMFG) containing the RGD domain and anticancer drug, bleomycin. Human breast cancer cells (MDA-MB-231) were incubated with 0.3 nM concentration of GNP–drug complex for 16 h prior to irradiation with a 2 Gy single fraction of 6 MV X-rays. After the treatment, cells were trypsinized and seeded in 60 mm dishes for clonogenic assay. Damage to DNA was probed using immunofluorescence assay. Results Cancer cells internalized with the GNP–drug complex had a 32 ± 9% decrease in cell survival and statistically significant enhancement in DNA (deoxyribonucleic acid) damage as compared to control cells (irradiated with no GNPs) after receiving a radiation dose of 2 Gy with 6 MV photons. Conclusions The experimental results demonstrate that GNP-mediated chemoradiation has the potential to improve cancer care in the near future through enhancement of the local radiation dose and controlled delivery of anticancer drugs.
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spelling doaj.art-0631bb869e1846829f92ee58393d7ed12022-12-21T18:50:46ZengBMCCancer Nanotechnology1868-69581868-69662018-05-019111410.1186/s12645-018-0039-3Gold nanoparticle mediated combined cancer therapyCelina Yang0Kyle Bromma1Caterina Di Ciano-Oliveira2Gaetano Zafarana3Monique van Prooijen4Devika B. Chithrani5Department of Physics, Ryerson UniversityDepartment of Physics and Astronomy, University of VictoriaKeenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s HospitalSTTARR Innovation CentreDepartment of Radiation Physics, Princess Margaret Cancer CentreDepartment of Physics, Ryerson UniversityAbstract Background The combined use of radiation therapy and chemotherapy is commonly being used in cancer treatment. The side effects of the treatment can be further minimized through targeted delivery of anticancer drugs and local enhancement of the radiation dose. Gold nanoparticles (GNPs) can play a significant role in this regard since GNPs can be used as radiation dose enhancers and anticancer drug carriers. Anticancer drug, bleomycin, was chosen as the model drug, since it could be easily conjugated onto GNPs through the gold–thiol bond. Methods Gold nanoparticles of size 10 nm were synthesized using the citrate reduction method. The surface of The GNPs was modified with a peptide sequence (CKKKKKKGGRGDMFG) containing the RGD domain and anticancer drug, bleomycin. Human breast cancer cells (MDA-MB-231) were incubated with 0.3 nM concentration of GNP–drug complex for 16 h prior to irradiation with a 2 Gy single fraction of 6 MV X-rays. After the treatment, cells were trypsinized and seeded in 60 mm dishes for clonogenic assay. Damage to DNA was probed using immunofluorescence assay. Results Cancer cells internalized with the GNP–drug complex had a 32 ± 9% decrease in cell survival and statistically significant enhancement in DNA (deoxyribonucleic acid) damage as compared to control cells (irradiated with no GNPs) after receiving a radiation dose of 2 Gy with 6 MV photons. Conclusions The experimental results demonstrate that GNP-mediated chemoradiation has the potential to improve cancer care in the near future through enhancement of the local radiation dose and controlled delivery of anticancer drugs.http://link.springer.com/article/10.1186/s12645-018-0039-3Gold nanoparticlesDrug deliveryRadiation dose enhancerCombined therapyDNA damage
spellingShingle Celina Yang
Kyle Bromma
Caterina Di Ciano-Oliveira
Gaetano Zafarana
Monique van Prooijen
Devika B. Chithrani
Gold nanoparticle mediated combined cancer therapy
Cancer Nanotechnology
Gold nanoparticles
Drug delivery
Radiation dose enhancer
Combined therapy
DNA damage
title Gold nanoparticle mediated combined cancer therapy
title_full Gold nanoparticle mediated combined cancer therapy
title_fullStr Gold nanoparticle mediated combined cancer therapy
title_full_unstemmed Gold nanoparticle mediated combined cancer therapy
title_short Gold nanoparticle mediated combined cancer therapy
title_sort gold nanoparticle mediated combined cancer therapy
topic Gold nanoparticles
Drug delivery
Radiation dose enhancer
Combined therapy
DNA damage
url http://link.springer.com/article/10.1186/s12645-018-0039-3
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AT kylebromma goldnanoparticlemediatedcombinedcancertherapy
AT caterinadicianooliveira goldnanoparticlemediatedcombinedcancertherapy
AT gaetanozafarana goldnanoparticlemediatedcombinedcancertherapy
AT moniquevanprooijen goldnanoparticlemediatedcombinedcancertherapy
AT devikabchithrani goldnanoparticlemediatedcombinedcancertherapy