Octaarginine-modified gold nanoparticles enhance the radiosensitivity of human colorectal cancer cell line LS180 to megavoltage radiation

Xuyang Zhang,1 Hao Wang,1 Jonathan Andrew Coulter,2 Ruijie Yang1 1Department of Radiation Oncology, Peking University Third Hospital, Beijing, China; 2School of Pharmacy, Queen’s University of Belfast, Belfast, UK Background: This study investigated the effectiveness and underpi...

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Autores principales:	Zhang XY, Wang H, Coulter JA, Yang R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8059d6e582cc48dd845e3de927bb968c
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spelling	oai:doaj.org-article:8059d6e582cc48dd845e3de927bb968c2021-12-02T02:27:00ZOctaarginine-modified gold nanoparticles enhance the radiosensitivity of human colorectal cancer cell line LS180 to megavoltage radiation1178-2013https://doaj.org/article/8059d6e582cc48dd845e3de927bb968c2018-06-01T00:00:00Zhttps://www.dovepress.com/octaarginine-modified-gold-nanoparticles-enhance-the-radiosensitivity--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xuyang Zhang,1 Hao Wang,1 Jonathan Andrew Coulter,2 Ruijie Yang1 1Department of Radiation Oncology, Peking University Third Hospital, Beijing, China; 2School of Pharmacy, Queen’s University of Belfast, Belfast, UK Background: This study investigated the effectiveness and underpinning mechanisms of radiosensitization using octaarginine (R8)-modified gold nanoparticle–poly(ethylene glycol) (GNP-PEG-R8) in colorectal cancer cell line LS180 to megavoltage radiotherapy in vitro. Method: In-house synthesized GNP-PEG was characterized by transmission electron microscopy, dynamic light scattering, ultraviolet–visible spectrophotometry, and X-ray photoelectron spectroscopy. Inductively coupled plasma mass spectroscopy was used to quantify internalization. Direct cytotoxicity was established using the Cell Counting Kit-8, while radiosensitivity was determined using the gold standard in vitro clonogenic assay. Cell-cycle distribution, apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were analyzed by flow cytometry, further exploring the key mechanisms driving GNP-PEG-R8 radiosensitization. Results: The core GNP diameter was 6.3±1.1 nm (mean±SD). Following functionalization, the hydrodynamic diameter increased to 19.7±2.8 nm and 27.8±1.8 nm for GNP-PEG and GNP-PEG-R8, with respective surface plasmon resonance peaks of 515 nm and 525 nm. Furthermore, incorporation of the R8 significantly increased nanoparticle internalization compared to GNP-PEG (p<0.001) over a 1 h treatment period. Functionalized GNPs confer little cytotoxicity below 400 nM. In clonogenic assays, radiation combined with GNP-PEG-R8 induced a significant reduction in colony formation compared with radiation alone, generating a sensitizer enhancement ratio of 1.59. Furthermore, GNP-PEG-R8 plus radiation predominantly induced cell-cycle arrest in the G2/M phase, increasing G2/M stalling by an additional 10% over GNP-PEG, markedly promoting apoptosis (p<0.001). Finally, ROS levels and alterations in MMP were investigated, indicating a highly significant (p<0.001) change in both parameters following the combined treatment of GNP-PEG-R8 and radiation over radiation alone. Conclusion: R8-modified GNPs were efficiently internalized by LS180 cells, exhibiting minimal cytotoxicity. This yielded significant radiosensitization in response to megavoltage radiation. GNP-PEG-R8 may enhance radiosensitivity by arresting cell cycle and inducing apoptosis, with elevated ROS identified as the likely initiator. Keywords: gold nanoparticles, octaarginine, colorectal cancer, megavoltage radiotherapy, mechanisms, radiosensitizationZhang XYWang HCoulter JAYang RDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3541-3552 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zhang XY Wang H Coulter JA Yang R Octaarginine-modified gold nanoparticles enhance the radiosensitivity of human colorectal cancer cell line LS180 to megavoltage radiation
description	Xuyang Zhang,1 Hao Wang,1 Jonathan Andrew Coulter,2 Ruijie Yang1 1Department of Radiation Oncology, Peking University Third Hospital, Beijing, China; 2School of Pharmacy, Queen’s University of Belfast, Belfast, UK Background: This study investigated the effectiveness and underpinning mechanisms of radiosensitization using octaarginine (R8)-modified gold nanoparticle–poly(ethylene glycol) (GNP-PEG-R8) in colorectal cancer cell line LS180 to megavoltage radiotherapy in vitro. Method: In-house synthesized GNP-PEG was characterized by transmission electron microscopy, dynamic light scattering, ultraviolet–visible spectrophotometry, and X-ray photoelectron spectroscopy. Inductively coupled plasma mass spectroscopy was used to quantify internalization. Direct cytotoxicity was established using the Cell Counting Kit-8, while radiosensitivity was determined using the gold standard in vitro clonogenic assay. Cell-cycle distribution, apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were analyzed by flow cytometry, further exploring the key mechanisms driving GNP-PEG-R8 radiosensitization. Results: The core GNP diameter was 6.3±1.1 nm (mean±SD). Following functionalization, the hydrodynamic diameter increased to 19.7±2.8 nm and 27.8±1.8 nm for GNP-PEG and GNP-PEG-R8, with respective surface plasmon resonance peaks of 515 nm and 525 nm. Furthermore, incorporation of the R8 significantly increased nanoparticle internalization compared to GNP-PEG (p<0.001) over a 1 h treatment period. Functionalized GNPs confer little cytotoxicity below 400 nM. In clonogenic assays, radiation combined with GNP-PEG-R8 induced a significant reduction in colony formation compared with radiation alone, generating a sensitizer enhancement ratio of 1.59. Furthermore, GNP-PEG-R8 plus radiation predominantly induced cell-cycle arrest in the G2/M phase, increasing G2/M stalling by an additional 10% over GNP-PEG, markedly promoting apoptosis (p<0.001). Finally, ROS levels and alterations in MMP were investigated, indicating a highly significant (p<0.001) change in both parameters following the combined treatment of GNP-PEG-R8 and radiation over radiation alone. Conclusion: R8-modified GNPs were efficiently internalized by LS180 cells, exhibiting minimal cytotoxicity. This yielded significant radiosensitization in response to megavoltage radiation. GNP-PEG-R8 may enhance radiosensitivity by arresting cell cycle and inducing apoptosis, with elevated ROS identified as the likely initiator. Keywords: gold nanoparticles, octaarginine, colorectal cancer, megavoltage radiotherapy, mechanisms, radiosensitization
format	article
author	Zhang XY Wang H Coulter JA Yang R
author_facet	Zhang XY Wang H Coulter JA Yang R
author_sort	Zhang XY
title	Octaarginine-modified gold nanoparticles enhance the radiosensitivity of human colorectal cancer cell line LS180 to megavoltage radiation
title_short	Octaarginine-modified gold nanoparticles enhance the radiosensitivity of human colorectal cancer cell line LS180 to megavoltage radiation
title_full	Octaarginine-modified gold nanoparticles enhance the radiosensitivity of human colorectal cancer cell line LS180 to megavoltage radiation
title_fullStr	Octaarginine-modified gold nanoparticles enhance the radiosensitivity of human colorectal cancer cell line LS180 to megavoltage radiation
title_full_unstemmed	Octaarginine-modified gold nanoparticles enhance the radiosensitivity of human colorectal cancer cell line LS180 to megavoltage radiation
title_sort	octaarginine-modified gold nanoparticles enhance the radiosensitivity of human colorectal cancer cell line ls180 to megavoltage radiation
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/8059d6e582cc48dd845e3de927bb968c
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Octaarginine-modified gold nanoparticles enhance the radiosensitivity of human colorectal cancer cell line LS180 to megavoltage radiation

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