Polysaccharide-modified nanoparticles with intelligent CD44 receptor targeting ability for gene delivery

Wen Jen Lin,1,2 Wei Chi Lee1 1School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; 2Drug Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan Background: Hyaluronic acid (HA) and chondroitin sulfate (CD) are endogenous polysaccharides. In...

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Autores principales:	Lin WJ, Lee WC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	hyaluronic acid chondroitin sulfate poly(lactide-co-glycolide) gene delivery CD44 receptor. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/4848fb9cb86e45debd8ca9b4c62fb2e0
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spelling	oai:doaj.org-article:4848fb9cb86e45debd8ca9b4c62fb2e02021-12-02T02:57:17ZPolysaccharide-modified nanoparticles with intelligent CD44 receptor targeting ability for gene delivery1178-2013https://doaj.org/article/4848fb9cb86e45debd8ca9b4c62fb2e02018-07-01T00:00:00Zhttps://www.dovepress.com/polysaccharide-modified-nanoparticles-with-intelligent-cd44-receptor-t-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Wen Jen Lin,1,2 Wei Chi Lee1 1School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; 2Drug Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan Background: Hyaluronic acid (HA) and chondroitin sulfate (CD) are endogenous polysaccharides. In recent years, they have aroused the interest of scientists because of specific binding to CD44 receptors, which are overexpressed in several types of tumors. Methods: In this study, HA- and CD-modified poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymers were synthesized and applied to encapsulate 1,2-Dioleoyl-3-trimethylammonium-propane (DOTAP)/pDNA (D/P) lipoplex as CD44 receptor targeting gene delivery nanoparticles (NPs). Results: The particle size of CD-PEG-PLGA-D/P (186.8 ± 21.7 nm) was smaller than that of HA-PEG-PLGA-D/P (270.2 ± 13.8 nm), with narrow size distribution, and both HA-PEG-PLGA-D/P NPs and CD-PEG-PLGA NPs possessed negative zeta potentials (-39.63 ± 5.44 mV and -38.9 ± 2.0 mV, respectively), which prevent erythrocytes from agglutination. Both NPs exhibited pH-dependent release and had faster release in pH 4.0 than in pH 7.4. Generally, the CD-PEG-PLGA-D/P NPs possessed less cytotoxicity than HA-PEG-PLGA-D/P NPs. The D/P-loaded HA-PEG-PLGA and CD-PEG-PLGA NPs expressed significantly higher transfection in CD44 high-expressed U87 (30.1% ± 2.1% and 40.7% ± 4.3%, respectively) than in CD44-negative HepG2 (3.3% ± 1.5% and 1.4% ± 1.0%, respectively) (p < 0.001). It was revealed that the endocytosis of HA-PEG-PLGA-D/P NPs was majorly dominated by macropinocytosis and the endocytosis of CD-PEG-PLGA-D/P NPs was dominated by clathrin-mediated endocytosis pathway (p < 0.001). Conclusion: The high selectivity to CD44-positive U87 cancer cells and low cytotoxicity in L929 normal cells assured the promising potential of CD-PEG-PLGA NPs as gene delivery nano-carriers. Keywords: hyaluronic acid, chondroitin sulfate, poly(lactide-co-glycolide)Lin WJLee WCDove Medical Pressarticlehyaluronic acidchondroitin sulfatepoly(lactide-co-glycolide)gene deliveryCD44 receptor.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3989-4002 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	hyaluronic acid chondroitin sulfate poly(lactide-co-glycolide) gene delivery CD44 receptor. Medicine (General) R5-920
spellingShingle	hyaluronic acid chondroitin sulfate poly(lactide-co-glycolide) gene delivery CD44 receptor. Medicine (General) R5-920 Lin WJ Lee WC Polysaccharide-modified nanoparticles with intelligent CD44 receptor targeting ability for gene delivery
description	Wen Jen Lin,1,2 Wei Chi Lee1 1School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; 2Drug Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan Background: Hyaluronic acid (HA) and chondroitin sulfate (CD) are endogenous polysaccharides. In recent years, they have aroused the interest of scientists because of specific binding to CD44 receptors, which are overexpressed in several types of tumors. Methods: In this study, HA- and CD-modified poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymers were synthesized and applied to encapsulate 1,2-Dioleoyl-3-trimethylammonium-propane (DOTAP)/pDNA (D/P) lipoplex as CD44 receptor targeting gene delivery nanoparticles (NPs). Results: The particle size of CD-PEG-PLGA-D/P (186.8 ± 21.7 nm) was smaller than that of HA-PEG-PLGA-D/P (270.2 ± 13.8 nm), with narrow size distribution, and both HA-PEG-PLGA-D/P NPs and CD-PEG-PLGA NPs possessed negative zeta potentials (-39.63 ± 5.44 mV and -38.9 ± 2.0 mV, respectively), which prevent erythrocytes from agglutination. Both NPs exhibited pH-dependent release and had faster release in pH 4.0 than in pH 7.4. Generally, the CD-PEG-PLGA-D/P NPs possessed less cytotoxicity than HA-PEG-PLGA-D/P NPs. The D/P-loaded HA-PEG-PLGA and CD-PEG-PLGA NPs expressed significantly higher transfection in CD44 high-expressed U87 (30.1% ± 2.1% and 40.7% ± 4.3%, respectively) than in CD44-negative HepG2 (3.3% ± 1.5% and 1.4% ± 1.0%, respectively) (p < 0.001). It was revealed that the endocytosis of HA-PEG-PLGA-D/P NPs was majorly dominated by macropinocytosis and the endocytosis of CD-PEG-PLGA-D/P NPs was dominated by clathrin-mediated endocytosis pathway (p < 0.001). Conclusion: The high selectivity to CD44-positive U87 cancer cells and low cytotoxicity in L929 normal cells assured the promising potential of CD-PEG-PLGA NPs as gene delivery nano-carriers. Keywords: hyaluronic acid, chondroitin sulfate, poly(lactide-co-glycolide)
format	article
author	Lin WJ Lee WC
author_facet	Lin WJ Lee WC
author_sort	Lin WJ
title	Polysaccharide-modified nanoparticles with intelligent CD44 receptor targeting ability for gene delivery
title_short	Polysaccharide-modified nanoparticles with intelligent CD44 receptor targeting ability for gene delivery
title_full	Polysaccharide-modified nanoparticles with intelligent CD44 receptor targeting ability for gene delivery
title_fullStr	Polysaccharide-modified nanoparticles with intelligent CD44 receptor targeting ability for gene delivery
title_full_unstemmed	Polysaccharide-modified nanoparticles with intelligent CD44 receptor targeting ability for gene delivery
title_sort	polysaccharide-modified nanoparticles with intelligent cd44 receptor targeting ability for gene delivery
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/4848fb9cb86e45debd8ca9b4c62fb2e0
work_keys_str_mv	AT linwj polysaccharidemodifiednanoparticleswithintelligentcd44receptortargetingabilityforgenedelivery AT leewc polysaccharidemodifiednanoparticleswithintelligentcd44receptortargetingabilityforgenedelivery
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Polysaccharide-modified nanoparticles with intelligent CD44 receptor targeting ability for gene delivery

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