Olaparib nanoparticles potentiated radiosensitization effects on lung cancer

Min Wu,1,* Jing Liu,1,* ChuanFei Hu,1 Dong Li,1 Juan Yang,1 ZhouXue Wu,1 LingLin Yang,1 Yue Chen,2 ShaoZhi Fu,1 JingBo Wu1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; 2Department of Nuclear Medicine, The Affiliated Hospital of Southwest Me...

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Autores principales:	Wu M, Liu J, Hu C, Li D, Yang J, Wu Z, Yang L, Chen Y, Fu S, Wu J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Lung cancer Nanoparticles Olaparib Radio-sensitization Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5868c667c94840848edc7c2eadb8bcf6
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spelling	oai:doaj.org-article:5868c667c94840848edc7c2eadb8bcf62021-12-02T07:56:25ZOlaparib nanoparticles potentiated radiosensitization effects on lung cancer1178-2013https://doaj.org/article/5868c667c94840848edc7c2eadb8bcf62018-12-01T00:00:00Zhttps://www.dovepress.com/olaparib-nanoparticles-potentiated-radiosensitization-effects-on-lung--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Min Wu,1,* Jing Liu,1,* ChuanFei Hu,1 Dong Li,1 Juan Yang,1 ZhouXue Wu,1 LingLin Yang,1 Yue Chen,2 ShaoZhi Fu,1 JingBo Wu1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; 2Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China *These authors contributed equally to this work Background: Poly (ADP-ribose) polymerase (PARP) is a key enzyme in the repair process of DNA strand breaks (DSBs). Olaparib (Ola) is a PARP inhibitor that is involved in arresting PARP release from radiotherapy (RT)-induced damaged DNA to potentiate the effect of RT. Although the underlying mechanisms for the radiosensitization effects of Ola are well understood in vitro, the radiosensitization effects in vivo are still unclear. Moreover, poor water solubility and severe toxicity are two major impediments for the clinical success of Ola.Materials and methods: Here, we developed olaparib nanoparticles (Ola-NPs) and investigated their radiosensitization mechanisms and toxicity using human non-small-cell lung cancer xenograft models in mice.Results: The prepared Ola-NPs showed a mean size of 31.96±1.54 nm and a lower polydispersity index of about 0.126±0.014. In addition, the sensitization enhancement ratio of Ola-NPs (3.81) was much higher than that of free Ola (1.66). The combination of Ola-NPs and RT (Ola-NPs + RT) significantly inhibited tumor growth and prolonged survival in mice. The mechanism of enhanced antitumor efficacy might be related to the inhibition of DSB repair and the promotion of cell apoptosis in vivo. No additional toxicity caused by Ola-NPs was observed.Conclusion: This study demonstrated the principle of using Ola-NPs as a potent radiosensitizer to improve the therapeutic effect of RT relative to free Ola (P<0.05 in all cases). Keywords: lung cancer, nanoparticles, olaparib, radiosensitizationWu MLiu JHu CLi DYang JWu ZYang LChen YFu SWu JDove Medical PressarticleLung cancerNanoparticlesOlaparibRadio-sensitizationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 8461-8472 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Lung cancer Nanoparticles Olaparib Radio-sensitization Medicine (General) R5-920
spellingShingle	Lung cancer Nanoparticles Olaparib Radio-sensitization Medicine (General) R5-920 Wu M Liu J Hu C Li D Yang J Wu Z Yang L Chen Y Fu S Wu J Olaparib nanoparticles potentiated radiosensitization effects on lung cancer
description	Min Wu,1,* Jing Liu,1,* ChuanFei Hu,1 Dong Li,1 Juan Yang,1 ZhouXue Wu,1 LingLin Yang,1 Yue Chen,2 ShaoZhi Fu,1 JingBo Wu1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; 2Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China *These authors contributed equally to this work Background: Poly (ADP-ribose) polymerase (PARP) is a key enzyme in the repair process of DNA strand breaks (DSBs). Olaparib (Ola) is a PARP inhibitor that is involved in arresting PARP release from radiotherapy (RT)-induced damaged DNA to potentiate the effect of RT. Although the underlying mechanisms for the radiosensitization effects of Ola are well understood in vitro, the radiosensitization effects in vivo are still unclear. Moreover, poor water solubility and severe toxicity are two major impediments for the clinical success of Ola.Materials and methods: Here, we developed olaparib nanoparticles (Ola-NPs) and investigated their radiosensitization mechanisms and toxicity using human non-small-cell lung cancer xenograft models in mice.Results: The prepared Ola-NPs showed a mean size of 31.96±1.54 nm and a lower polydispersity index of about 0.126±0.014. In addition, the sensitization enhancement ratio of Ola-NPs (3.81) was much higher than that of free Ola (1.66). The combination of Ola-NPs and RT (Ola-NPs + RT) significantly inhibited tumor growth and prolonged survival in mice. The mechanism of enhanced antitumor efficacy might be related to the inhibition of DSB repair and the promotion of cell apoptosis in vivo. No additional toxicity caused by Ola-NPs was observed.Conclusion: This study demonstrated the principle of using Ola-NPs as a potent radiosensitizer to improve the therapeutic effect of RT relative to free Ola (P<0.05 in all cases). Keywords: lung cancer, nanoparticles, olaparib, radiosensitization
format	article
author	Wu M Liu J Hu C Li D Yang J Wu Z Yang L Chen Y Fu S Wu J
author_facet	Wu M Liu J Hu C Li D Yang J Wu Z Yang L Chen Y Fu S Wu J
author_sort	Wu M
title	Olaparib nanoparticles potentiated radiosensitization effects on lung cancer
title_short	Olaparib nanoparticles potentiated radiosensitization effects on lung cancer
title_full	Olaparib nanoparticles potentiated radiosensitization effects on lung cancer
title_fullStr	Olaparib nanoparticles potentiated radiosensitization effects on lung cancer
title_full_unstemmed	Olaparib nanoparticles potentiated radiosensitization effects on lung cancer
title_sort	olaparib nanoparticles potentiated radiosensitization effects on lung cancer
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/5868c667c94840848edc7c2eadb8bcf6
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Olaparib nanoparticles potentiated radiosensitization effects on lung cancer

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