Mithramycin-loaded mPEG-PLGA nanoparticles exert potent antitumor efficacy against pancreatic carcinoma

Xu-Jie Liu, Liang Li, Xiu-Jun Liu, Yi Li, Chun-Yan Zhao, Rui-Qi Wang, Yong-Su Zhen Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China Abstract: Previous studies have shown that mithramycin A (MIT...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Liu XJ, Li L, Li Y, Zhao CY, Wang RQ, Zhen YS
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	mithramycin pancreatic cancer mPEG-PLGA nanoparticles Sp1 CD47 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7efd93d61fd84b6cbc26f61a53b33b43
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7efd93d61fd84b6cbc26f61a53b33b43
record_format	dspace
spelling	oai:doaj.org-article:7efd93d61fd84b6cbc26f61a53b33b432021-12-02T04:28:16ZMithramycin-loaded mPEG-PLGA nanoparticles exert potent antitumor efficacy against pancreatic carcinoma1178-2013https://doaj.org/article/7efd93d61fd84b6cbc26f61a53b33b432017-07-01T00:00:00Zhttps://www.dovepress.com/mithramycin-loaded-mpeg-plga-nanoparticles-exert-potent-antitumor-effi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xu-Jie Liu, Liang Li, Xiu-Jun Liu, Yi Li, Chun-Yan Zhao, Rui-Qi Wang, Yong-Su Zhen Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China Abstract: Previous studies have shown that mithramycin A (MIT) is a promising candidate for the treatment of pancreatic carcinoma through inhibiting transcription factor Sp1. However, systemic toxicities may limit its clinical application. Here, we report a rationally designed formulation of MIT-loaded nanoparticles (MIT-NPs) with a small size and sustained release for improved passive targeting and enhanced therapeutic efficacy. Nearly spherical MIT-NPs with a mean particle size of 25.0±4.6 nm were prepared by encapsulating MIT into methoxy poly(ethylene glycol)-block-poly(D,L-lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles (NPs) with drug loading of 2.11%±0.51%. The in vitro release of the MIT-NPs lasted for >48 h with a sustained-release pattern. The cytotoxicity of MIT-NPs to human pancreatic cancer BxPC-3 and MIA Paca-2 cells was comparable to that of free MIT. Determined by flow cytometry and confocal microscopy, the NPs internalized into the cells quickly and efficiently, reaching the peak level at 1–2 h. In vivo fluorescence imaging showed that the prepared NPs were gradually accumulated in BxPC-3 and MIA Paca-2 xenografts and retained for 168 h. The fluorescence intensity in both BxPC-3 and MIA Paca-2 tumors was much stronger than that of various tested organs. Therapeutic efficacy was evaluated with the poorly permeable BxPC-3 pancreatic carcinoma xenograft model. At a well-tolerated dose of 2 mg/kg, MIT-NPs suppressed BxPC-3 tumor growth by 96%. Compared at an equivalent dose, MIT-NPs exerted significantly higher therapeutic effect than free MIT (86% versus 51%, P<0.01). Moreover, the treatment of MIT and MIT-NPs reduced the expression level of oncogene c-Myc regulated by Sp1, and notably, both of them decreased the protein level of CD47. In summary, the novel formulation of MIT-NPs shows highly therapeutic efficacy against pancreatic carcinoma xenograft. In addition, MIT-NPs can downregulate CD47 expression, implying that it might play a positive role in cancer immunotherapy. Keywords: mithramycin, pancreatic cancer, mPEG-PLGA nanoparticles, Sp1, CD47Liu XJLi LLiu XJLi YZhao CYWang RQZhen YSDove Medical Pressarticlemithramycinpancreatic cancermPEG-PLGA nanoparticlesSp1CD47Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 5255-5269 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	mithramycin pancreatic cancer mPEG-PLGA nanoparticles Sp1 CD47 Medicine (General) R5-920
spellingShingle	mithramycin pancreatic cancer mPEG-PLGA nanoparticles Sp1 CD47 Medicine (General) R5-920 Liu XJ Li L Liu XJ Li Y Zhao CY Wang RQ Zhen YS Mithramycin-loaded mPEG-PLGA nanoparticles exert potent antitumor efficacy against pancreatic carcinoma
description	Xu-Jie Liu, Liang Li, Xiu-Jun Liu, Yi Li, Chun-Yan Zhao, Rui-Qi Wang, Yong-Su Zhen Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China Abstract: Previous studies have shown that mithramycin A (MIT) is a promising candidate for the treatment of pancreatic carcinoma through inhibiting transcription factor Sp1. However, systemic toxicities may limit its clinical application. Here, we report a rationally designed formulation of MIT-loaded nanoparticles (MIT-NPs) with a small size and sustained release for improved passive targeting and enhanced therapeutic efficacy. Nearly spherical MIT-NPs with a mean particle size of 25.0±4.6 nm were prepared by encapsulating MIT into methoxy poly(ethylene glycol)-block-poly(D,L-lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles (NPs) with drug loading of 2.11%±0.51%. The in vitro release of the MIT-NPs lasted for >48 h with a sustained-release pattern. The cytotoxicity of MIT-NPs to human pancreatic cancer BxPC-3 and MIA Paca-2 cells was comparable to that of free MIT. Determined by flow cytometry and confocal microscopy, the NPs internalized into the cells quickly and efficiently, reaching the peak level at 1–2 h. In vivo fluorescence imaging showed that the prepared NPs were gradually accumulated in BxPC-3 and MIA Paca-2 xenografts and retained for 168 h. The fluorescence intensity in both BxPC-3 and MIA Paca-2 tumors was much stronger than that of various tested organs. Therapeutic efficacy was evaluated with the poorly permeable BxPC-3 pancreatic carcinoma xenograft model. At a well-tolerated dose of 2 mg/kg, MIT-NPs suppressed BxPC-3 tumor growth by 96%. Compared at an equivalent dose, MIT-NPs exerted significantly higher therapeutic effect than free MIT (86% versus 51%, P<0.01). Moreover, the treatment of MIT and MIT-NPs reduced the expression level of oncogene c-Myc regulated by Sp1, and notably, both of them decreased the protein level of CD47. In summary, the novel formulation of MIT-NPs shows highly therapeutic efficacy against pancreatic carcinoma xenograft. In addition, MIT-NPs can downregulate CD47 expression, implying that it might play a positive role in cancer immunotherapy. Keywords: mithramycin, pancreatic cancer, mPEG-PLGA nanoparticles, Sp1, CD47
format	article
author	Liu XJ Li L Liu XJ Li Y Zhao CY Wang RQ Zhen YS
author_facet	Liu XJ Li L Liu XJ Li Y Zhao CY Wang RQ Zhen YS
author_sort	Liu XJ
title	Mithramycin-loaded mPEG-PLGA nanoparticles exert potent antitumor efficacy against pancreatic carcinoma
title_short	Mithramycin-loaded mPEG-PLGA nanoparticles exert potent antitumor efficacy against pancreatic carcinoma
title_full	Mithramycin-loaded mPEG-PLGA nanoparticles exert potent antitumor efficacy against pancreatic carcinoma
title_fullStr	Mithramycin-loaded mPEG-PLGA nanoparticles exert potent antitumor efficacy against pancreatic carcinoma
title_full_unstemmed	Mithramycin-loaded mPEG-PLGA nanoparticles exert potent antitumor efficacy against pancreatic carcinoma
title_sort	mithramycin-loaded mpeg-plga nanoparticles exert potent antitumor efficacy against pancreatic carcinoma
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/7efd93d61fd84b6cbc26f61a53b33b43
work_keys_str_mv	AT liuxj mithramycinloadedmpegplgananoparticlesexertpotentantitumorefficacyagainstpancreaticcarcinoma AT lil mithramycinloadedmpegplgananoparticlesexertpotentantitumorefficacyagainstpancreaticcarcinoma AT liuxj mithramycinloadedmpegplgananoparticlesexertpotentantitumorefficacyagainstpancreaticcarcinoma AT liy mithramycinloadedmpegplgananoparticlesexertpotentantitumorefficacyagainstpancreaticcarcinoma AT zhaocy mithramycinloadedmpegplgananoparticlesexertpotentantitumorefficacyagainstpancreaticcarcinoma AT wangrq mithramycinloadedmpegplgananoparticlesexertpotentantitumorefficacyagainstpancreaticcarcinoma AT zhenys mithramycinloadedmpegplgananoparticlesexertpotentantitumorefficacyagainstpancreaticcarcinoma
_version_	1718401196355485696

Mithramycin-loaded mPEG-PLGA nanoparticles exert potent antitumor efficacy against pancreatic carcinoma

Ejemplares similares