Enhanced Anti-Cancer Effect of Folate-Conjugated Olaparib Nanoparticles Combined with Radiotherapy in Cervical Carcinoma

Dong Li,1,* Chuanfei Hu,1,* Juan Yang,1 Yin Liao,1 Yue Chen,2,3 Shao Zhi Fu,1 Jing Bo Wu1,3 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, People’s Republic of China; 2Department of Nuclear Medicine, The Affiliated Hospital of Southwest Med...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Li D, Hu C, Yang J, Liao Y, Chen Y, Fu SZ, Wu JB
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	olaparib cervical cancer folate anti-cancer effect active targeting Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5367e9eacc244d46b609e8353cc3759e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5367e9eacc244d46b609e8353cc3759e
record_format	dspace
spelling	oai:doaj.org-article:5367e9eacc244d46b609e8353cc3759e2021-12-02T15:12:06ZEnhanced Anti-Cancer Effect of Folate-Conjugated Olaparib Nanoparticles Combined with Radiotherapy in Cervical Carcinoma1178-2013https://doaj.org/article/5367e9eacc244d46b609e8353cc3759e2020-12-01T00:00:00Zhttps://www.dovepress.com/enhanced-anti-cancer-effect-of-folate-conjugated-olaparib-nanoparticle-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Dong Li,1,* Chuanfei Hu,1,* Juan Yang,1 Yin Liao,1 Yue Chen,2,3 Shao Zhi Fu,1 Jing Bo Wu1,3 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, People’s Republic of China; 2Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, People’s Republic of China; 3Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Bo WuDepartment of Oncology, The Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Luzhou 646000, People’s Republic of ChinaEmail wjb6147@163.comShao Zhi FuDepartment of Oncology, The Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Luzhou 646000, People’s Republic of ChinaTel +86 830 316 5698Fax +86 830 316 5690Email shaozhifu513@163.comBackground: Radiotherapy (RT), one of the main treatments for cervical cancer, has tremendous potential for improvement in the efficacy. Poly (ADP-ribose) polymerase (PARP) is a key enzyme in the repair of DNA strand breaks (DSB). Olaparib (Ola) is a PARP inhibitor that is involved in preventing the release of PARP from RT-induced damaged DNA to potentiate the effect of RT. Although the basic mechanism of Ola’s radiosensitization is well known, the radiosensitization mechanism of its nanomedicine is still unclear. In addition, the lack of tumor tissue targeting is a major obstacle for the clinical success of Ola.Materials and Methods: In this study, we developed folate-conjugated active targeting olaparib nanoparticles (ATO) and investigated the anti-tumor effect of ATO combined with radiotherapy (RT) in nude mice using cervical cancer xenograft models. We used folate (FA)-conjugated poly (ϵ-caprolactone)-poly (ethyleneglycol)-poly (e-caprolactone) (PCEC) copolymer to prepare ATO via emulsification/solvent diffusion. Further, we evaluated ATO particle size, potential, encapsulation efficiency, and in vitro release characteristics, and evaluated the shape of ATO via transmission electron microscopy (TEM). We then performed MTT and cell uptake assays to detect cytotoxicity and targeting uptake in vitro. We investigated the anti-tumor properties of ATO in vivo by apoptosis test, 18 F-FDG PET/CT, and immunohistochemical analysis. Finally, the xenografted tumor in nude mice was subjected to RT and/or ATO treatment.Results: The results confirmed that ATO in combination with RT significantly inhibited tumor growth and prolonged survival time of tumor-bearing mice. This may be related to the inhibition of tumor proliferation and DNA damage repair and induction of cell apoptosis in vivo.Conclusion: The ATO developed in this study may represent a novel formulation for olaparib delivery and have promising potential for treating tumors with an over-expression of folate receptors.Keywords: olaparib, cervical cancer, folate, anti-cancer effect, active targetingLi DHu CYang JLiao YChen YFu SZWu JBDove Medical Pressarticleolaparibcervical cancerfolateanti-cancer effectactive targetingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 10045-10058 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	olaparib cervical cancer folate anti-cancer effect active targeting Medicine (General) R5-920
spellingShingle	olaparib cervical cancer folate anti-cancer effect active targeting Medicine (General) R5-920 Li D Hu C Yang J Liao Y Chen Y Fu SZ Wu JB Enhanced Anti-Cancer Effect of Folate-Conjugated Olaparib Nanoparticles Combined with Radiotherapy in Cervical Carcinoma
description	Dong Li,1,* Chuanfei Hu,1,* Juan Yang,1 Yin Liao,1 Yue Chen,2,3 Shao Zhi Fu,1 Jing Bo Wu1,3 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, People’s Republic of China; 2Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, People’s Republic of China; 3Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Bo WuDepartment of Oncology, The Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Luzhou 646000, People’s Republic of ChinaEmail wjb6147@163.comShao Zhi FuDepartment of Oncology, The Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Luzhou 646000, People’s Republic of ChinaTel +86 830 316 5698Fax +86 830 316 5690Email shaozhifu513@163.comBackground: Radiotherapy (RT), one of the main treatments for cervical cancer, has tremendous potential for improvement in the efficacy. Poly (ADP-ribose) polymerase (PARP) is a key enzyme in the repair of DNA strand breaks (DSB). Olaparib (Ola) is a PARP inhibitor that is involved in preventing the release of PARP from RT-induced damaged DNA to potentiate the effect of RT. Although the basic mechanism of Ola’s radiosensitization is well known, the radiosensitization mechanism of its nanomedicine is still unclear. In addition, the lack of tumor tissue targeting is a major obstacle for the clinical success of Ola.Materials and Methods: In this study, we developed folate-conjugated active targeting olaparib nanoparticles (ATO) and investigated the anti-tumor effect of ATO combined with radiotherapy (RT) in nude mice using cervical cancer xenograft models. We used folate (FA)-conjugated poly (ϵ-caprolactone)-poly (ethyleneglycol)-poly (e-caprolactone) (PCEC) copolymer to prepare ATO via emulsification/solvent diffusion. Further, we evaluated ATO particle size, potential, encapsulation efficiency, and in vitro release characteristics, and evaluated the shape of ATO via transmission electron microscopy (TEM). We then performed MTT and cell uptake assays to detect cytotoxicity and targeting uptake in vitro. We investigated the anti-tumor properties of ATO in vivo by apoptosis test, 18 F-FDG PET/CT, and immunohistochemical analysis. Finally, the xenografted tumor in nude mice was subjected to RT and/or ATO treatment.Results: The results confirmed that ATO in combination with RT significantly inhibited tumor growth and prolonged survival time of tumor-bearing mice. This may be related to the inhibition of tumor proliferation and DNA damage repair and induction of cell apoptosis in vivo.Conclusion: The ATO developed in this study may represent a novel formulation for olaparib delivery and have promising potential for treating tumors with an over-expression of folate receptors.Keywords: olaparib, cervical cancer, folate, anti-cancer effect, active targeting
format	article
author	Li D Hu C Yang J Liao Y Chen Y Fu SZ Wu JB
author_facet	Li D Hu C Yang J Liao Y Chen Y Fu SZ Wu JB
author_sort	Li D
title	Enhanced Anti-Cancer Effect of Folate-Conjugated Olaparib Nanoparticles Combined with Radiotherapy in Cervical Carcinoma
title_short	Enhanced Anti-Cancer Effect of Folate-Conjugated Olaparib Nanoparticles Combined with Radiotherapy in Cervical Carcinoma
title_full	Enhanced Anti-Cancer Effect of Folate-Conjugated Olaparib Nanoparticles Combined with Radiotherapy in Cervical Carcinoma
title_fullStr	Enhanced Anti-Cancer Effect of Folate-Conjugated Olaparib Nanoparticles Combined with Radiotherapy in Cervical Carcinoma
title_full_unstemmed	Enhanced Anti-Cancer Effect of Folate-Conjugated Olaparib Nanoparticles Combined with Radiotherapy in Cervical Carcinoma
title_sort	enhanced anti-cancer effect of folate-conjugated olaparib nanoparticles combined with radiotherapy in cervical carcinoma
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/5367e9eacc244d46b609e8353cc3759e
work_keys_str_mv	AT lid enhancedanticancereffectoffolateconjugatedolaparibnanoparticlescombinedwithradiotherapyincervicalcarcinoma AT huc enhancedanticancereffectoffolateconjugatedolaparibnanoparticlescombinedwithradiotherapyincervicalcarcinoma AT yangj enhancedanticancereffectoffolateconjugatedolaparibnanoparticlescombinedwithradiotherapyincervicalcarcinoma AT liaoy enhancedanticancereffectoffolateconjugatedolaparibnanoparticlescombinedwithradiotherapyincervicalcarcinoma AT cheny enhancedanticancereffectoffolateconjugatedolaparibnanoparticlescombinedwithradiotherapyincervicalcarcinoma AT fusz enhancedanticancereffectoffolateconjugatedolaparibnanoparticlescombinedwithradiotherapyincervicalcarcinoma AT wujb enhancedanticancereffectoffolateconjugatedolaparibnanoparticlescombinedwithradiotherapyincervicalcarcinoma
_version_	1718387628262293504

Enhanced Anti-Cancer Effect of Folate-Conjugated Olaparib Nanoparticles Combined with Radiotherapy in Cervical Carcinoma

Ejemplares similares