Inhibited Metastasis and Amplified Chemotherapeutic Effects by Epigene-Transfection Based on a Tumor-Targeting Nanoparticle

Mengzhu Wang,1 Zhigang Wang,1 Bin Qiao,1 Jin Cao,1 Luya Quan,1 Yuanli Luo,1 Hanwen Qi,2 Xiaowen Zhong,1 Yubei He,1 Xianquan Zhang,1,3 Lan Hao1 1Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 2Th...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Wang M, Wang Z, Qiao B, Cao J, Quan L, Luo Y, Qi H, Zhong X, He Y, Zhang X, Hao L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	targeted epigenotherapy metastasis drug resistance multimodality imaging breast cancer Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/18a6217c86094a6d921dbb97cc5ff332
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:18a6217c86094a6d921dbb97cc5ff332
record_format	dspace
spelling	oai:doaj.org-article:18a6217c86094a6d921dbb97cc5ff3322021-12-02T09:30:45ZInhibited Metastasis and Amplified Chemotherapeutic Effects by Epigene-Transfection Based on a Tumor-Targeting Nanoparticle1178-2013https://doaj.org/article/18a6217c86094a6d921dbb97cc5ff3322020-06-01T00:00:00Zhttps://www.dovepress.com/inhibited-metastasis-and-amplified-chemotherapeutic-effects-by-epigene-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Mengzhu Wang,1 Zhigang Wang,1 Bin Qiao,1 Jin Cao,1 Luya Quan,1 Yuanli Luo,1 Hanwen Qi,2 Xiaowen Zhong,1 Yubei He,1 Xianquan Zhang,1,3 Lan Hao1 1Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 2The A. Gary Anderson Graduate School of Management, University of California, Riverside, Riverside, CA, 92521, USA; 3Cardiothoracic Surgery Department, Chongqing Hygeia Cancer Hospital, Chongqing, 401331, People’s Republic of ChinaCorrespondence: Lan HaoInstitute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, 1# Yixueyuan Road, Yuzhong District, Chongqing, People’s Republic of ChinaTel +86 15823291038Email lanhao5@cqmu.edu.cnXianquan ZhangChongqing Hygeia Cancer Hospital, No. 222, Sixian Road, University Town, Shapingba District, Chongqing 401331, People’s Republic of ChinaTel +86 13996286125Email xqzhng@163.comPurpose: Tumor metastasis and drug resistance have always been vital aspects to cancer mortality and prognosis. To compromise metastasis and drug resistance, a nanoparticle IPPD-PHF2 (IR780/PLGA-PEI(Dox)-PHF2) has been engineered to accomplish efficient targeted epigenotherapy forced by PHF2-induced MET (mesenchymal to epithelial transition).Materials and Methods: IPPD-PHF2 nanoparticle was synthesized and characterized by several analytical techniques. The transfection efficiency of IPP-PHF2 (IR780/PLGA-PEI-PHF2) was compared with PP-PHF2 (PLGA-PEI-PHF2) in vitro by WB and in vivo by IHC, and the cytotoxicity of IPP was compared with Lipo2000 in vitro by CCK8 assay. The inhibition of cancer cell migration caused by PHF2-upregulation was tested by wound healing assay, and the enhanced chemotherapeutic sensitivity was detected by flow cytometry. Tumor-targeting property of IPPD-PHF2 was proved by fluorescent imaging in vivo with MDA-MB-231 tumor-bearing nude mice. Except for fluorescent imaging ability, considerable photoacoustic signals of IPPD-PHF2 at tumor sites were verified. The anti-tumor activity of IPPD-PHF2 was investigated using in vivo human breast cancer MDA-MB-231 cell models.Results: Tumor-targeting nanoparticle IPPD-PHF2 had an average size of about 319.2 nm, a stable zeta potential at about 38 mV. The encapsulation efficiency of doxorubicin was around 39.28%, and the adsorption capacity of plasmids was about 64.804 μg/mg. Significant up-regulation of PHF2 induced MET and caused reduced migration as well as enhanced chemotherapeutic sensitivity. Either IPPD (IR780/PLGA-PEI(Dox)) or IPP-PHF2 (IR780/PLGA-PEI-PHF2) presented minor therapeutic effects, whereas IPPD-PHF2 specifically accumulated within tumors, showed extraordinary transfection efficiency specifically in tumor sites, acted as inhibitors of metastasis and proliferation, and presented good multimodality imaging potentials in vivo.Conclusion: IPPD-PHF2 NPs is a promising tool to bring epigenotherapy into a more practical era, and the potential application of harm-free multimodality imaging guidance is of great value.Keywords: targeted epigenotherapy, metastasis, drug resistance, multimodality imaging, breast cancerWang MWang ZQiao BCao JQuan LLuo YQi HZhong XHe YZhang XHao LDove Medical Pressarticletargeted epigenotherapymetastasisdrug resistancemultimodality imagingbreast cancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 4483-4500 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	targeted epigenotherapy metastasis drug resistance multimodality imaging breast cancer Medicine (General) R5-920
spellingShingle	targeted epigenotherapy metastasis drug resistance multimodality imaging breast cancer Medicine (General) R5-920 Wang M Wang Z Qiao B Cao J Quan L Luo Y Qi H Zhong X He Y Zhang X Hao L Inhibited Metastasis and Amplified Chemotherapeutic Effects by Epigene-Transfection Based on a Tumor-Targeting Nanoparticle
description	Mengzhu Wang,1 Zhigang Wang,1 Bin Qiao,1 Jin Cao,1 Luya Quan,1 Yuanli Luo,1 Hanwen Qi,2 Xiaowen Zhong,1 Yubei He,1 Xianquan Zhang,1,3 Lan Hao1 1Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 2The A. Gary Anderson Graduate School of Management, University of California, Riverside, Riverside, CA, 92521, USA; 3Cardiothoracic Surgery Department, Chongqing Hygeia Cancer Hospital, Chongqing, 401331, People’s Republic of ChinaCorrespondence: Lan HaoInstitute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, 1# Yixueyuan Road, Yuzhong District, Chongqing, People’s Republic of ChinaTel +86 15823291038Email lanhao5@cqmu.edu.cnXianquan ZhangChongqing Hygeia Cancer Hospital, No. 222, Sixian Road, University Town, Shapingba District, Chongqing 401331, People’s Republic of ChinaTel +86 13996286125Email xqzhng@163.comPurpose: Tumor metastasis and drug resistance have always been vital aspects to cancer mortality and prognosis. To compromise metastasis and drug resistance, a nanoparticle IPPD-PHF2 (IR780/PLGA-PEI(Dox)-PHF2) has been engineered to accomplish efficient targeted epigenotherapy forced by PHF2-induced MET (mesenchymal to epithelial transition).Materials and Methods: IPPD-PHF2 nanoparticle was synthesized and characterized by several analytical techniques. The transfection efficiency of IPP-PHF2 (IR780/PLGA-PEI-PHF2) was compared with PP-PHF2 (PLGA-PEI-PHF2) in vitro by WB and in vivo by IHC, and the cytotoxicity of IPP was compared with Lipo2000 in vitro by CCK8 assay. The inhibition of cancer cell migration caused by PHF2-upregulation was tested by wound healing assay, and the enhanced chemotherapeutic sensitivity was detected by flow cytometry. Tumor-targeting property of IPPD-PHF2 was proved by fluorescent imaging in vivo with MDA-MB-231 tumor-bearing nude mice. Except for fluorescent imaging ability, considerable photoacoustic signals of IPPD-PHF2 at tumor sites were verified. The anti-tumor activity of IPPD-PHF2 was investigated using in vivo human breast cancer MDA-MB-231 cell models.Results: Tumor-targeting nanoparticle IPPD-PHF2 had an average size of about 319.2 nm, a stable zeta potential at about 38 mV. The encapsulation efficiency of doxorubicin was around 39.28%, and the adsorption capacity of plasmids was about 64.804 μg/mg. Significant up-regulation of PHF2 induced MET and caused reduced migration as well as enhanced chemotherapeutic sensitivity. Either IPPD (IR780/PLGA-PEI(Dox)) or IPP-PHF2 (IR780/PLGA-PEI-PHF2) presented minor therapeutic effects, whereas IPPD-PHF2 specifically accumulated within tumors, showed extraordinary transfection efficiency specifically in tumor sites, acted as inhibitors of metastasis and proliferation, and presented good multimodality imaging potentials in vivo.Conclusion: IPPD-PHF2 NPs is a promising tool to bring epigenotherapy into a more practical era, and the potential application of harm-free multimodality imaging guidance is of great value.Keywords: targeted epigenotherapy, metastasis, drug resistance, multimodality imaging, breast cancer
format	article
author	Wang M Wang Z Qiao B Cao J Quan L Luo Y Qi H Zhong X He Y Zhang X Hao L
author_facet	Wang M Wang Z Qiao B Cao J Quan L Luo Y Qi H Zhong X He Y Zhang X Hao L
author_sort	Wang M
title	Inhibited Metastasis and Amplified Chemotherapeutic Effects by Epigene-Transfection Based on a Tumor-Targeting Nanoparticle
title_short	Inhibited Metastasis and Amplified Chemotherapeutic Effects by Epigene-Transfection Based on a Tumor-Targeting Nanoparticle
title_full	Inhibited Metastasis and Amplified Chemotherapeutic Effects by Epigene-Transfection Based on a Tumor-Targeting Nanoparticle
title_fullStr	Inhibited Metastasis and Amplified Chemotherapeutic Effects by Epigene-Transfection Based on a Tumor-Targeting Nanoparticle
title_full_unstemmed	Inhibited Metastasis and Amplified Chemotherapeutic Effects by Epigene-Transfection Based on a Tumor-Targeting Nanoparticle
title_sort	inhibited metastasis and amplified chemotherapeutic effects by epigene-transfection based on a tumor-targeting nanoparticle
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/18a6217c86094a6d921dbb97cc5ff332
work_keys_str_mv	AT wangm inhibitedmetastasisandamplifiedchemotherapeuticeffectsbyepigenetransfectionbasedonatumortargetingnanoparticle AT wangz inhibitedmetastasisandamplifiedchemotherapeuticeffectsbyepigenetransfectionbasedonatumortargetingnanoparticle AT qiaob inhibitedmetastasisandamplifiedchemotherapeuticeffectsbyepigenetransfectionbasedonatumortargetingnanoparticle AT caoj inhibitedmetastasisandamplifiedchemotherapeuticeffectsbyepigenetransfectionbasedonatumortargetingnanoparticle AT quanl inhibitedmetastasisandamplifiedchemotherapeuticeffectsbyepigenetransfectionbasedonatumortargetingnanoparticle AT luoy inhibitedmetastasisandamplifiedchemotherapeuticeffectsbyepigenetransfectionbasedonatumortargetingnanoparticle AT qih inhibitedmetastasisandamplifiedchemotherapeuticeffectsbyepigenetransfectionbasedonatumortargetingnanoparticle AT zhongx inhibitedmetastasisandamplifiedchemotherapeuticeffectsbyepigenetransfectionbasedonatumortargetingnanoparticle AT hey inhibitedmetastasisandamplifiedchemotherapeuticeffectsbyepigenetransfectionbasedonatumortargetingnanoparticle AT zhangx inhibitedmetastasisandamplifiedchemotherapeuticeffectsbyepigenetransfectionbasedonatumortargetingnanoparticle AT haol inhibitedmetastasisandamplifiedchemotherapeuticeffectsbyepigenetransfectionbasedonatumortargetingnanoparticle
_version_	1718398051531358208

Inhibited Metastasis and Amplified Chemotherapeutic Effects by Epigene-Transfection Based on a Tumor-Targeting Nanoparticle

Ejemplares similares