Self-Assembled Dual-Targeted Epirubicin-Hybrid Polydopamine Nanoparticles for Combined Chemo-Photothermal Therapy of Triple-Negative Breast Cancer

Xiang Li,1,* Qian Zou,1,* Jing Zhang,2 Peng Zhang,2 Xiong Zhou,1 Satya Siva Kishan Yalamarty,3 Xinli Liang,2 Yali Liu,4 Qin Zheng,2 Jianqing Gao5 1State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchan...

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Autores principales:	Li X, Zou Q, Zhang J, Zhang P, Zhou X, Yalamarty SSK, Liang X, Liu Y, Zheng Q, Gao J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	polydopamine nanoparticles l-cysteine epirubicin pharmacokinetics triple-negative breast cancer Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f0ea62371ceb4531bcce865800fbb5e7
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id	oai:doaj.org-article:f0ea62371ceb4531bcce865800fbb5e7
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	polydopamine nanoparticles l-cysteine epirubicin pharmacokinetics triple-negative breast cancer Medicine (General) R5-920
spellingShingle	polydopamine nanoparticles l-cysteine epirubicin pharmacokinetics triple-negative breast cancer Medicine (General) R5-920 Li X Zou Q Zhang J Zhang P Zhou X Yalamarty SSK Liang X Liu Y Zheng Q Gao J Self-Assembled Dual-Targeted Epirubicin-Hybrid Polydopamine Nanoparticles for Combined Chemo-Photothermal Therapy of Triple-Negative Breast Cancer
description	Xiang Li,1,* Qian Zou,1,* Jing Zhang,2 Peng Zhang,2 Xiong Zhou,1 Satya Siva Kishan Yalamarty,3 Xinli Liang,2 Yali Liu,4 Qin Zheng,2 Jianqing Gao5 1State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, Jiangxi, People’s Republic of China; 2Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi, People’s Republic of China; 3Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA; 4College of Science and Technology, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi, People’s Republic of China; 5Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing ZhangKey Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi, People’s Republic of ChinaTel/Fax +86 791 87118658Email 20101036@jxutcm.edu.cnPurpose: Folic acid and cyclic arginylglycylaspartic acid peptides were introduced to the surface of negatively charged lipid-coated hybrid polydopamine-cysteine cores for the delivery of epirubicin (EPI) (E/PCF-NPs). The combined chemo-photothermal therapy using E/PCF-NPs for triple-negative breast cancer was evaluated.Materials and Methods: The temperature elevation and thermal toxicity of nanoparticles were studied. The morphology and properties of E/PCF-NPs were characterized by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. Physicochemical properties, including particle size, zeta potential, drug loading, entrapment efficiency (EE%), stability and in vitro release, were determined. The cell viability, reactive oxygen species (ROS) levels, ratios of oxidized nicotinamide adenine dinucleotide to its reduced form (NAD+/NADH), apoptosis assays, and cellular uptake of E/PCF-NPs were determined on 4T1 cells. Pharmacokinetic studies and tissue distributions were performed and detected by an ultra-high performance liquid chromatography/mass spectrometry system. The antitumor effects of E/PCF-NPs under near-infrared (NIR) laser irradiation were also evaluated.Results: The sphere-like morphology of E/PCF-NPs showed a high EE%, uniform size of 106.7 nm, remarkable stability, and highly improved cytotoxicity under NIR laser, when compared to that of photothermal treatment alone. In vitro release of EPI from E/PCF-NPs was pH sensitive, and a greater response was achieved under NIR laser irradiation. Compared to chemotherapy or photothermal treatment alone, the combined treatment in vitro significantly inhibited the survival rate of 4T1 cells to 17.7%, induced ROS generation, and reduced NAD+/NADH significantly. Treatment with E/PCF-NPs under irradiation induced 4T1 cell apoptosis in approximately 93.6% cells. In vitro cellular uptake of E/PCF-NPs was time-dependent. The long-circulating and higher tumor accumulation of E/PCF-NPs resulted in complete ablation of breast tumor tissue through the enhanced photothermal effect by NIR laser irradiation-mediated cell apoptosis.Conclusion: E/PCF-NPs show enhanced anti-cancer effects due to synergistic effects of chemotherapy with photothermal therapy and may be potential therapeutic agents for cancer treatment.Keywords: polydopamine nanoparticles, L-cysteine, epirubicin, pharmacokinetics, triple-negative breast cancer
format	article
author	Li X Zou Q Zhang J Zhang P Zhou X Yalamarty SSK Liang X Liu Y Zheng Q Gao J
author_facet	Li X Zou Q Zhang J Zhang P Zhou X Yalamarty SSK Liang X Liu Y Zheng Q Gao J
author_sort	Li X
title	Self-Assembled Dual-Targeted Epirubicin-Hybrid Polydopamine Nanoparticles for Combined Chemo-Photothermal Therapy of Triple-Negative Breast Cancer
title_short	Self-Assembled Dual-Targeted Epirubicin-Hybrid Polydopamine Nanoparticles for Combined Chemo-Photothermal Therapy of Triple-Negative Breast Cancer
title_full	Self-Assembled Dual-Targeted Epirubicin-Hybrid Polydopamine Nanoparticles for Combined Chemo-Photothermal Therapy of Triple-Negative Breast Cancer
title_fullStr	Self-Assembled Dual-Targeted Epirubicin-Hybrid Polydopamine Nanoparticles for Combined Chemo-Photothermal Therapy of Triple-Negative Breast Cancer
title_full_unstemmed	Self-Assembled Dual-Targeted Epirubicin-Hybrid Polydopamine Nanoparticles for Combined Chemo-Photothermal Therapy of Triple-Negative Breast Cancer
title_sort	self-assembled dual-targeted epirubicin-hybrid polydopamine nanoparticles for combined chemo-photothermal therapy of triple-negative breast cancer
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/f0ea62371ceb4531bcce865800fbb5e7
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spelling	oai:doaj.org-article:f0ea62371ceb4531bcce865800fbb5e72021-12-02T11:13:19ZSelf-Assembled Dual-Targeted Epirubicin-Hybrid Polydopamine Nanoparticles for Combined Chemo-Photothermal Therapy of Triple-Negative Breast Cancer1178-2013https://doaj.org/article/f0ea62371ceb4531bcce865800fbb5e72020-09-01T00:00:00Zhttps://www.dovepress.com/self-assembled-dual-targeted-epirubicin-hybrid-polydopamine-nanopartic-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiang Li,1,* Qian Zou,1,* Jing Zhang,2 Peng Zhang,2 Xiong Zhou,1 Satya Siva Kishan Yalamarty,3 Xinli Liang,2 Yali Liu,4 Qin Zheng,2 Jianqing Gao5 1State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, Jiangxi, People’s Republic of China; 2Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi, People’s Republic of China; 3Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA; 4College of Science and Technology, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi, People’s Republic of China; 5Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing ZhangKey Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, Jiangxi, People’s Republic of ChinaTel/Fax +86 791 87118658Email 20101036@jxutcm.edu.cnPurpose: Folic acid and cyclic arginylglycylaspartic acid peptides were introduced to the surface of negatively charged lipid-coated hybrid polydopamine-cysteine cores for the delivery of epirubicin (EPI) (E/PCF-NPs). The combined chemo-photothermal therapy using E/PCF-NPs for triple-negative breast cancer was evaluated.Materials and Methods: The temperature elevation and thermal toxicity of nanoparticles were studied. The morphology and properties of E/PCF-NPs were characterized by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. Physicochemical properties, including particle size, zeta potential, drug loading, entrapment efficiency (EE%), stability and in vitro release, were determined. The cell viability, reactive oxygen species (ROS) levels, ratios of oxidized nicotinamide adenine dinucleotide to its reduced form (NAD+/NADH), apoptosis assays, and cellular uptake of E/PCF-NPs were determined on 4T1 cells. Pharmacokinetic studies and tissue distributions were performed and detected by an ultra-high performance liquid chromatography/mass spectrometry system. The antitumor effects of E/PCF-NPs under near-infrared (NIR) laser irradiation were also evaluated.Results: The sphere-like morphology of E/PCF-NPs showed a high EE%, uniform size of 106.7 nm, remarkable stability, and highly improved cytotoxicity under NIR laser, when compared to that of photothermal treatment alone. In vitro release of EPI from E/PCF-NPs was pH sensitive, and a greater response was achieved under NIR laser irradiation. Compared to chemotherapy or photothermal treatment alone, the combined treatment in vitro significantly inhibited the survival rate of 4T1 cells to 17.7%, induced ROS generation, and reduced NAD+/NADH significantly. Treatment with E/PCF-NPs under irradiation induced 4T1 cell apoptosis in approximately 93.6% cells. In vitro cellular uptake of E/PCF-NPs was time-dependent. The long-circulating and higher tumor accumulation of E/PCF-NPs resulted in complete ablation of breast tumor tissue through the enhanced photothermal effect by NIR laser irradiation-mediated cell apoptosis.Conclusion: E/PCF-NPs show enhanced anti-cancer effects due to synergistic effects of chemotherapy with photothermal therapy and may be potential therapeutic agents for cancer treatment.Keywords: polydopamine nanoparticles, L-cysteine, epirubicin, pharmacokinetics, triple-negative breast cancerLi XZou QZhang JZhang PZhou XYalamarty SSKLiang XLiu YZheng QGao JDove Medical Pressarticlepolydopamine nanoparticlesl-cysteineepirubicinpharmacokineticstriple-negative breast cancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 6791-6811 (2020)

Self-Assembled Dual-Targeted Epirubicin-Hybrid Polydopamine Nanoparticles for Combined Chemo-Photothermal Therapy of Triple-Negative Breast Cancer

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