Redox-sensitive iodinated polymersomes carrying histone deacetylase inhibitor as a dual-functional nano-radiosensitizer for enhanced radiotherapy of breast cancer

Radiotherapy (RT) is a frequently used means in clinical tumor treatment. The outcome of RT varies, however, to a great extent, due to RT resistance or intolerable dose, which might be resolved by the development of radio-sensitizing strategies. Here, we report redox-sensitive iodinated polymersomes...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zhehong Zhu, Manran Wu, Juan Sun, Zhengyuan Huangfu, Lingling Yin, Weipeng Yong, Jing Sun, Guanglin Wang, Fenghua Meng, Zhiyuan Zhong
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	radiotherapy polymersomes saha drug delivery spect Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/7ab1bdf9134343d89b77a5cfc268abef
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7ab1bdf9134343d89b77a5cfc268abef
record_format	dspace
spelling	oai:doaj.org-article:7ab1bdf9134343d89b77a5cfc268abef2021-11-11T14:23:41ZRedox-sensitive iodinated polymersomes carrying histone deacetylase inhibitor as a dual-functional nano-radiosensitizer for enhanced radiotherapy of breast cancer1071-75441521-046410.1080/10717544.2021.1995080https://doaj.org/article/7ab1bdf9134343d89b77a5cfc268abef2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/10717544.2021.1995080https://doaj.org/toc/1071-7544https://doaj.org/toc/1521-0464Radiotherapy (RT) is a frequently used means in clinical tumor treatment. The outcome of RT varies, however, to a great extent, due to RT resistance or intolerable dose, which might be resolved by the development of radio-sensitizing strategies. Here, we report redox-sensitive iodinated polymersomes (RIP) carrying histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA, vorinostat), as a new dual-functional nano-radiosensitizer for breast cancer radiotherapy. SAHA-loaded RIP (RIP-SAHA) with a size of about 101 nm exhibited good colloidal stability while the reduction-activated release of SAHA, giving rise to better antitumor effect to 4T1 breast carcinoma cells than free SAHA. Accordingly, RIP-SAHA combined with a 4 Gy dose of X-ray radiation led to significantly enhanced suppression of 4T1 cells compared with SAHA combined 4 Gy of X-ray radiation, as a result of enhanced DNA damage and impeded DNA damage repair. The pharmacokinetics and biodistribution studies by single-photon emission computed tomography (SPECT) with 125I-labeled SAHA (125I-SAHA) showed a 17.3-fold longer circulation and 237.7-fold better tumor accumulation of RIP-SAHA over SAHA. The systemic administration of RIP-SAHA greatly sensitized radiotherapy of subcutaneous 4T1 breast tumors and brought about significant inhibition of tumor growth, without causing damages to major organs, compared with radiotherapy alone. RIP not only enhanced SAHA delivery but also acted as a radiosensitizer. RIP-SAHA emerges as a smart dual-functional nano-radiosensitizer to effectively enhance tumor radiotherapy.Zhehong ZhuManran WuJuan SunZhengyuan HuangfuLingling YinWeipeng YongJing SunGuanglin WangFenghua MengZhiyuan ZhongTaylor & Francis Grouparticleradiotherapypolymersomessahadrug deliveryspectTherapeutics. PharmacologyRM1-950ENDrug Delivery, Vol 28, Iss 1, Pp 2301-2309 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	radiotherapy polymersomes saha drug delivery spect Therapeutics. Pharmacology RM1-950
spellingShingle	radiotherapy polymersomes saha drug delivery spect Therapeutics. Pharmacology RM1-950 Zhehong Zhu Manran Wu Juan Sun Zhengyuan Huangfu Lingling Yin Weipeng Yong Jing Sun Guanglin Wang Fenghua Meng Zhiyuan Zhong Redox-sensitive iodinated polymersomes carrying histone deacetylase inhibitor as a dual-functional nano-radiosensitizer for enhanced radiotherapy of breast cancer
description	Radiotherapy (RT) is a frequently used means in clinical tumor treatment. The outcome of RT varies, however, to a great extent, due to RT resistance or intolerable dose, which might be resolved by the development of radio-sensitizing strategies. Here, we report redox-sensitive iodinated polymersomes (RIP) carrying histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA, vorinostat), as a new dual-functional nano-radiosensitizer for breast cancer radiotherapy. SAHA-loaded RIP (RIP-SAHA) with a size of about 101 nm exhibited good colloidal stability while the reduction-activated release of SAHA, giving rise to better antitumor effect to 4T1 breast carcinoma cells than free SAHA. Accordingly, RIP-SAHA combined with a 4 Gy dose of X-ray radiation led to significantly enhanced suppression of 4T1 cells compared with SAHA combined 4 Gy of X-ray radiation, as a result of enhanced DNA damage and impeded DNA damage repair. The pharmacokinetics and biodistribution studies by single-photon emission computed tomography (SPECT) with 125I-labeled SAHA (125I-SAHA) showed a 17.3-fold longer circulation and 237.7-fold better tumor accumulation of RIP-SAHA over SAHA. The systemic administration of RIP-SAHA greatly sensitized radiotherapy of subcutaneous 4T1 breast tumors and brought about significant inhibition of tumor growth, without causing damages to major organs, compared with radiotherapy alone. RIP not only enhanced SAHA delivery but also acted as a radiosensitizer. RIP-SAHA emerges as a smart dual-functional nano-radiosensitizer to effectively enhance tumor radiotherapy.
format	article
author	Zhehong Zhu Manran Wu Juan Sun Zhengyuan Huangfu Lingling Yin Weipeng Yong Jing Sun Guanglin Wang Fenghua Meng Zhiyuan Zhong
author_facet	Zhehong Zhu Manran Wu Juan Sun Zhengyuan Huangfu Lingling Yin Weipeng Yong Jing Sun Guanglin Wang Fenghua Meng Zhiyuan Zhong
author_sort	Zhehong Zhu
title	Redox-sensitive iodinated polymersomes carrying histone deacetylase inhibitor as a dual-functional nano-radiosensitizer for enhanced radiotherapy of breast cancer
title_short	Redox-sensitive iodinated polymersomes carrying histone deacetylase inhibitor as a dual-functional nano-radiosensitizer for enhanced radiotherapy of breast cancer
title_full	Redox-sensitive iodinated polymersomes carrying histone deacetylase inhibitor as a dual-functional nano-radiosensitizer for enhanced radiotherapy of breast cancer
title_fullStr	Redox-sensitive iodinated polymersomes carrying histone deacetylase inhibitor as a dual-functional nano-radiosensitizer for enhanced radiotherapy of breast cancer
title_full_unstemmed	Redox-sensitive iodinated polymersomes carrying histone deacetylase inhibitor as a dual-functional nano-radiosensitizer for enhanced radiotherapy of breast cancer
title_sort	redox-sensitive iodinated polymersomes carrying histone deacetylase inhibitor as a dual-functional nano-radiosensitizer for enhanced radiotherapy of breast cancer
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/7ab1bdf9134343d89b77a5cfc268abef
work_keys_str_mv	AT zhehongzhu redoxsensitiveiodinatedpolymersomescarryinghistonedeacetylaseinhibitorasadualfunctionalnanoradiosensitizerforenhancedradiotherapyofbreastcancer AT manranwu redoxsensitiveiodinatedpolymersomescarryinghistonedeacetylaseinhibitorasadualfunctionalnanoradiosensitizerforenhancedradiotherapyofbreastcancer AT juansun redoxsensitiveiodinatedpolymersomescarryinghistonedeacetylaseinhibitorasadualfunctionalnanoradiosensitizerforenhancedradiotherapyofbreastcancer AT zhengyuanhuangfu redoxsensitiveiodinatedpolymersomescarryinghistonedeacetylaseinhibitorasadualfunctionalnanoradiosensitizerforenhancedradiotherapyofbreastcancer AT linglingyin redoxsensitiveiodinatedpolymersomescarryinghistonedeacetylaseinhibitorasadualfunctionalnanoradiosensitizerforenhancedradiotherapyofbreastcancer AT weipengyong redoxsensitiveiodinatedpolymersomescarryinghistonedeacetylaseinhibitorasadualfunctionalnanoradiosensitizerforenhancedradiotherapyofbreastcancer AT jingsun redoxsensitiveiodinatedpolymersomescarryinghistonedeacetylaseinhibitorasadualfunctionalnanoradiosensitizerforenhancedradiotherapyofbreastcancer AT guanglinwang redoxsensitiveiodinatedpolymersomescarryinghistonedeacetylaseinhibitorasadualfunctionalnanoradiosensitizerforenhancedradiotherapyofbreastcancer AT fenghuameng redoxsensitiveiodinatedpolymersomescarryinghistonedeacetylaseinhibitorasadualfunctionalnanoradiosensitizerforenhancedradiotherapyofbreastcancer AT zhiyuanzhong redoxsensitiveiodinatedpolymersomescarryinghistonedeacetylaseinhibitorasadualfunctionalnanoradiosensitizerforenhancedradiotherapyofbreastcancer
_version_	1718438949006868480

Redox-sensitive iodinated polymersomes carrying histone deacetylase inhibitor as a dual-functional nano-radiosensitizer for enhanced radiotherapy of breast cancer

Ejemplares similares