Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance

DanDan Zhang,1 Yan Yan Kong,1 Jia Hui Sun,1 Shao Jie Huo,1 Min Zhou,2 Yi Ling Gui,1 Xu Mu,1 Huan Chen,1 Shu Qin Yu,1 Qian Xu3 1Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 2School of Pharmacy, Jiangsu Food and...

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Autores principales:	Zhang DD, Kong YY, Sun JH, Huo SJ, Zhou M, Gui YL, Mu X, Chen H, Yu SQ, Xu Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Combination chemotherapy Co-delivery Multidrug resistance pH sensitive nanoparticle Intracellular precision release Nuclear drug delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/61af8ddee7e348469cd92241475d2fcf
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spelling	oai:doaj.org-article:61af8ddee7e348469cd92241475d2fcf2021-12-02T04:33:04ZCo-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance1178-2013https://doaj.org/article/61af8ddee7e348469cd92241475d2fcf2017-03-01T00:00:00Zhttps://www.dovepress.com/co-delivery-nanoparticles-with-characteristics-of-intracellular-precis-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013DanDan Zhang,1 Yan Yan Kong,1 Jia Hui Sun,1 Shao Jie Huo,1 Min Zhou,2 Yi Ling Gui,1 Xu Mu,1 Huan Chen,1 Shu Qin Yu,1 Qian Xu3 1Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 2School of Pharmacy, Jiangsu Food and Pharmaceutical Science College, Huai’an, 3Ministry of Education Key Laboratory of Environmental Medicine and Engineering, School of Public Health, Southeast University, Nanjing, People’s Republic of China Abstract: Combination chemotherapy in clinical practice has been generally accepted as a feasible strategy for overcoming multidrug resistance (MDR). Here, we designed and successfully prepared a co-delivery system named S-D1@L-D2 NPs, where denoted some smaller nanoparticles (NPs) carrying a drug doxorubicin (DOX) were loaded into a larger NP containing another drug (vincristine [VCR]) via water-in-oil-in-water double-emulsion solvent diffusion-evaporation method. Chitosan-alginate nanoparticles carrying DOX (CS-ALG-DOX NPs) with a smaller diameter of about 20 nm formed S-D1 NPs; vitamin E D-α-tocopheryl polyethylene glycol 1000 succinate-modified poly(lactic-co-glycolic acid) nanoparticles carrying VCR (TPGS-PLGA-VCR NPs) with a larger diameter of about 200 nm constituted L-D2 NPs. Some CS-ALG-DOX NPs loaded into TPGS-PLGA-VCR NPs formed CS-ALG-DOX@TPGS-PLGA-VCR NPs. Under the acidic environment of cytosol and endosome or lysosome in MDR cell, CS-ALG-DOX@TPGS-PLGA-VCR NPs released VCR and CS-ALG-DOX NPs. VCR could arrest cell cycles at metaphase by inhibiting microtubule polymerization in the cytoplasm. After CS-ALG-DOX NPs escaped from endosome, they entered the nucleus through the nuclear pore and released DOX in the intra-nuclear alkaline environment, which interacted with DNA to stop the replication of MDR cells. These results indicated that S-D1@L-D2 NPs was a co-delivery system of intracellular precision release loaded drugs with pH-sensitive characteristics. S-D1@L-D2 NPs could obviously enhance the in vitro cytotoxicity and the in vivo anticancer efficiency of co-delivery drugs, while reducing their adverse effects. Overall, S-D1@L-D2 NPs can be considered an innovative platform for the co-delivery drugs of clinical combination chemotherapy for the treatment of MDR tumor. Keywords: combination chemotherapy, co-delivery, multidrug resistance, pH-sensitive nanoparticle, intracellular precision release, nuclear drug deliveryZhang DDKong YYSun JHHuo SJZhou MGui YLMu XChen HYu SQXu QDove Medical PressarticleCombination chemotherapyCo-deliveryMultidrug resistancepH sensitive nanoparticleIntracellular precision releaseNuclear drug deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2081-2108 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Combination chemotherapy Co-delivery Multidrug resistance pH sensitive nanoparticle Intracellular precision release Nuclear drug delivery Medicine (General) R5-920
spellingShingle	Combination chemotherapy Co-delivery Multidrug resistance pH sensitive nanoparticle Intracellular precision release Nuclear drug delivery Medicine (General) R5-920 Zhang DD Kong YY Sun JH Huo SJ Zhou M Gui YL Mu X Chen H Yu SQ Xu Q Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance
description	DanDan Zhang,1 Yan Yan Kong,1 Jia Hui Sun,1 Shao Jie Huo,1 Min Zhou,2 Yi Ling Gui,1 Xu Mu,1 Huan Chen,1 Shu Qin Yu,1 Qian Xu3 1Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 2School of Pharmacy, Jiangsu Food and Pharmaceutical Science College, Huai’an, 3Ministry of Education Key Laboratory of Environmental Medicine and Engineering, School of Public Health, Southeast University, Nanjing, People’s Republic of China Abstract: Combination chemotherapy in clinical practice has been generally accepted as a feasible strategy for overcoming multidrug resistance (MDR). Here, we designed and successfully prepared a co-delivery system named S-D1@L-D2 NPs, where denoted some smaller nanoparticles (NPs) carrying a drug doxorubicin (DOX) were loaded into a larger NP containing another drug (vincristine [VCR]) via water-in-oil-in-water double-emulsion solvent diffusion-evaporation method. Chitosan-alginate nanoparticles carrying DOX (CS-ALG-DOX NPs) with a smaller diameter of about 20 nm formed S-D1 NPs; vitamin E D-α-tocopheryl polyethylene glycol 1000 succinate-modified poly(lactic-co-glycolic acid) nanoparticles carrying VCR (TPGS-PLGA-VCR NPs) with a larger diameter of about 200 nm constituted L-D2 NPs. Some CS-ALG-DOX NPs loaded into TPGS-PLGA-VCR NPs formed CS-ALG-DOX@TPGS-PLGA-VCR NPs. Under the acidic environment of cytosol and endosome or lysosome in MDR cell, CS-ALG-DOX@TPGS-PLGA-VCR NPs released VCR and CS-ALG-DOX NPs. VCR could arrest cell cycles at metaphase by inhibiting microtubule polymerization in the cytoplasm. After CS-ALG-DOX NPs escaped from endosome, they entered the nucleus through the nuclear pore and released DOX in the intra-nuclear alkaline environment, which interacted with DNA to stop the replication of MDR cells. These results indicated that S-D1@L-D2 NPs was a co-delivery system of intracellular precision release loaded drugs with pH-sensitive characteristics. S-D1@L-D2 NPs could obviously enhance the in vitro cytotoxicity and the in vivo anticancer efficiency of co-delivery drugs, while reducing their adverse effects. Overall, S-D1@L-D2 NPs can be considered an innovative platform for the co-delivery drugs of clinical combination chemotherapy for the treatment of MDR tumor. Keywords: combination chemotherapy, co-delivery, multidrug resistance, pH-sensitive nanoparticle, intracellular precision release, nuclear drug delivery
format	article
author	Zhang DD Kong YY Sun JH Huo SJ Zhou M Gui YL Mu X Chen H Yu SQ Xu Q
author_facet	Zhang DD Kong YY Sun JH Huo SJ Zhou M Gui YL Mu X Chen H Yu SQ Xu Q
author_sort	Zhang DD
title	Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance
title_short	Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance
title_full	Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance
title_fullStr	Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance
title_full_unstemmed	Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance
title_sort	co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/61af8ddee7e348469cd92241475d2fcf
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Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance

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