Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment

Changqie Pan,1–3,* Yuqing Liu,2,3,* Minyu Zhou,1 Wensheng Wang,4 Min Shi,1 Malcolm Xing,2,3,5 Wangjun Liao11Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China; 2Department of Mechanical Engineering, 3Department of Biochemistry and Medical Genetics, Univ...

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Autores principales:	Pan C, Liu Y, Zhou M, Wang W, Shi M, Xing M, Liao W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Theranostics Magnetic nanoparticle pH sensitivity Folate receptor targeting Breast cancer Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/80c471f209134221a281dd0d918ba3a7
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spelling	oai:doaj.org-article:80c471f209134221a281dd0d918ba3a72021-12-02T02:42:25ZTheranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment1178-2013https://doaj.org/article/80c471f209134221a281dd0d918ba3a72018-02-01T00:00:00Zhttps://www.dovepress.com/theranostic-ph-sensitive-nanoparticles-for-highly-efficient-targeted-d-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Changqie Pan,1–3,* Yuqing Liu,2,3,* Minyu Zhou,1 Wensheng Wang,4 Min Shi,1 Malcolm Xing,2,3,5 Wangjun Liao11Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China; 2Department of Mechanical Engineering, 3Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada; 4The Imaging Center, 999 Brain Hospital, Guangzhou, China; 5Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada*These authors contributed equally to this work Abstract: A multifunctional theranostic nanoplatform integrated with environmental responses has been developed rapidly over the past few years as a novel treatment strategy for several solid tumors. We synthesized pH-sensitive poly(β-thiopropionate) nanoparticles with a supermagnetic core and folic acid (FA) conjugation (FA-doxorubicin-iron oxide nanoparticles [FA-DOX@IONPs]) to deliver an antineoplastic drug, DOX, for the treatment of folate receptor (FR)-overexpressed breast cancer. In addition to an imaging function, the nanoparticles can release their payloads in response to an environment of pH 5, such as the acidic environment found in tumors. After chemical (1H nuclear magnetic resonance) and physical (morphology and supermagnetic) characterization, FA-DOX@IONPs were shown to demonstrate pH-dependent drug release profiles. Western blotting analysis revealed the expression of FRs in three breast cancer cell lines, MCF-7, BT549, and MD-MBA-231. The cell counting kit-8 assay and transmission electron microscopy showed that FA-DOX@IONPs had the strongest cytotoxicity against breast cancer cells, compared with free DOX and non-FR targeted nanoparticles (DOX@IONPs), and caused cellular apoptosis. The FA-DOX@IONP-mediated cellular uptake and intracellular internalization were clarified by fluorescence microscopy. FA-DOX@IONPs plus magnetic field treatment suppressed in vivo tumor growth in mice to a greater extent than either treatment alone; furthermore, the nanoparticles exerted no toxicity against healthy organs. Magnetic resonance imaging was successfully applied to monitor the nanoparticle accumulation. Our results suggest that theranostic pH-sensitive nanoparticles with dual targeting could enhance the available therapies for cancer. Keywords: theranostics, magnetic nanoparticle, pH sensitivity, folate receptor targeting, breast cancerPan CLiu YZhou MWang WShi MXing MLiao WDove Medical PressarticleTheranosticsMagnetic nanoparticlepH sensitivityFolate receptor targetingBreast cancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 1119-1137 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Theranostics Magnetic nanoparticle pH sensitivity Folate receptor targeting Breast cancer Medicine (General) R5-920
spellingShingle	Theranostics Magnetic nanoparticle pH sensitivity Folate receptor targeting Breast cancer Medicine (General) R5-920 Pan C Liu Y Zhou M Wang W Shi M Xing M Liao W Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment
description	Changqie Pan,1–3,* Yuqing Liu,2,3,* Minyu Zhou,1 Wensheng Wang,4 Min Shi,1 Malcolm Xing,2,3,5 Wangjun Liao11Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China; 2Department of Mechanical Engineering, 3Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada; 4The Imaging Center, 999 Brain Hospital, Guangzhou, China; 5Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada*These authors contributed equally to this work Abstract: A multifunctional theranostic nanoplatform integrated with environmental responses has been developed rapidly over the past few years as a novel treatment strategy for several solid tumors. We synthesized pH-sensitive poly(β-thiopropionate) nanoparticles with a supermagnetic core and folic acid (FA) conjugation (FA-doxorubicin-iron oxide nanoparticles [FA-DOX@IONPs]) to deliver an antineoplastic drug, DOX, for the treatment of folate receptor (FR)-overexpressed breast cancer. In addition to an imaging function, the nanoparticles can release their payloads in response to an environment of pH 5, such as the acidic environment found in tumors. After chemical (1H nuclear magnetic resonance) and physical (morphology and supermagnetic) characterization, FA-DOX@IONPs were shown to demonstrate pH-dependent drug release profiles. Western blotting analysis revealed the expression of FRs in three breast cancer cell lines, MCF-7, BT549, and MD-MBA-231. The cell counting kit-8 assay and transmission electron microscopy showed that FA-DOX@IONPs had the strongest cytotoxicity against breast cancer cells, compared with free DOX and non-FR targeted nanoparticles (DOX@IONPs), and caused cellular apoptosis. The FA-DOX@IONP-mediated cellular uptake and intracellular internalization were clarified by fluorescence microscopy. FA-DOX@IONPs plus magnetic field treatment suppressed in vivo tumor growth in mice to a greater extent than either treatment alone; furthermore, the nanoparticles exerted no toxicity against healthy organs. Magnetic resonance imaging was successfully applied to monitor the nanoparticle accumulation. Our results suggest that theranostic pH-sensitive nanoparticles with dual targeting could enhance the available therapies for cancer. Keywords: theranostics, magnetic nanoparticle, pH sensitivity, folate receptor targeting, breast cancer
format	article
author	Pan C Liu Y Zhou M Wang W Shi M Xing M Liao W
author_facet	Pan C Liu Y Zhou M Wang W Shi M Xing M Liao W
author_sort	Pan C
title	Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment
title_short	Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment
title_full	Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment
title_fullStr	Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment
title_full_unstemmed	Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment
title_sort	theranostic ph-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/80c471f209134221a281dd0d918ba3a7
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_version_	1718402229931606016

Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment

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