Inducing angiogenesis with the controlled release of nitric oxide from biodegradable and biocompatible copolymeric nanoparticles

Chungmo Yang,1,* Hae Hyun Hwang,2,* Soohyun Jeong,1 Deokwon Seo,1 Yoon Jeong,1 Dong Yun Lee,2,3 Kangwon Lee1,4 1Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea; 2Department of Bioengineering, C...

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Autores principales:	Yang C, Hwang HH, Jeong S, Seo D, Jeong Y, Lee DY, Lee K
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Nitric oxide Controlled release mPEG-PLGA nanoparticles Sprouting angiogenesis Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e892da029ba34f4fba983b3787417e4f
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spelling	oai:doaj.org-article:e892da029ba34f4fba983b3787417e4f2021-12-02T03:09:19ZInducing angiogenesis with the controlled release of nitric oxide from biodegradable and biocompatible copolymeric nanoparticles1178-2013https://doaj.org/article/e892da029ba34f4fba983b3787417e4f2018-10-01T00:00:00Zhttps://www.dovepress.com/inducing-angiogenesis-with-the-controlled-release-of-nitric-oxide-from-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Chungmo Yang,1,* Hae Hyun Hwang,2,* Soohyun Jeong,1 Deokwon Seo,1 Yoon Jeong,1 Dong Yun Lee,2,3 Kangwon Lee1,4 1Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea; 2Department of Bioengineering, College of Engineering, and BK21 PLUS Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul 04763, Republic of Korea; 3Institute of Nano Science & Technology (INST), Hanyang University, Seoul 04763, Republic of Korea; 4Advanced Institutes of Convergence Technology, Gyeonggi-do 16229, Republic of Korea *These authors contributed equally to this work Purpose: Nitric oxide (NO) can be clinically applied at low concentrations to regulate angiogenesis. However, studies using small molecule NO donors (N-diazeniumdiolate, S-nitrosothiol, etc) have yet to meet clinical requirements due to the short half-life and initial burst-release profile of NO donors. In this study, we report the feasibility of methoxy poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles (NPs) as NO-releasing polymers (NO-NPs) for inducing angiogenesis.Materials and methods: The mPEG–PLGA copolymers were synthesized by typical ring-opening polymerization of lactide, glycolide and mPEG as macroinitiators. Double emulsion methods were used to prepare mPEG–PLGA NPs incorporating hydrophilic NONOate (diethylenetriamine NONOate).Results: This liposomal NP encapsulates hydrophilic diethylenetriamine NONOate (70%±4%) more effectively than other previously reported materials. The application of NO-NPs at different ratios resulted in varying NO-release profiles with no significant cytotoxicity in various cell types: normal cells (fibroblasts, human umbilical vein endothelial cells and epithelial cells) and cancer cells (C6, A549 and MCF-7). The angiogenic potential of NO-NPs was confirmed in vitro by tube formation and ex vivo through an aorta ring assay. Tubular formation increased 189.8% in NO-NP–treated groups compared with that in the control group. Rat aorta exhibited robust sprouting angiogenesis in response to NO-NPs, indicating that NO was produced by polymeric NPs in a sustained manner.Conclusion: These findings provide initial results for an angiogenesis-related drug development platform by a straightforward method with biocompatible polymers. Keywords: mPEG-PLGA nanoparticles, sprouting angiogenesis, low concentration of nitric oxide, liposomal nanoparticles, amphiphilic polymersYang CHwang HHJeong SSeo DJeong YLee DYLee KDove Medical PressarticleNitric oxideControlled releasemPEG-PLGA nanoparticlesSprouting angiogenesisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 6517-6530 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nitric oxide Controlled release mPEG-PLGA nanoparticles Sprouting angiogenesis Medicine (General) R5-920
spellingShingle	Nitric oxide Controlled release mPEG-PLGA nanoparticles Sprouting angiogenesis Medicine (General) R5-920 Yang C Hwang HH Jeong S Seo D Jeong Y Lee DY Lee K Inducing angiogenesis with the controlled release of nitric oxide from biodegradable and biocompatible copolymeric nanoparticles
description	Chungmo Yang,1,* Hae Hyun Hwang,2,* Soohyun Jeong,1 Deokwon Seo,1 Yoon Jeong,1 Dong Yun Lee,2,3 Kangwon Lee1,4 1Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea; 2Department of Bioengineering, College of Engineering, and BK21 PLUS Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul 04763, Republic of Korea; 3Institute of Nano Science & Technology (INST), Hanyang University, Seoul 04763, Republic of Korea; 4Advanced Institutes of Convergence Technology, Gyeonggi-do 16229, Republic of Korea *These authors contributed equally to this work Purpose: Nitric oxide (NO) can be clinically applied at low concentrations to regulate angiogenesis. However, studies using small molecule NO donors (N-diazeniumdiolate, S-nitrosothiol, etc) have yet to meet clinical requirements due to the short half-life and initial burst-release profile of NO donors. In this study, we report the feasibility of methoxy poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles (NPs) as NO-releasing polymers (NO-NPs) for inducing angiogenesis.Materials and methods: The mPEG–PLGA copolymers were synthesized by typical ring-opening polymerization of lactide, glycolide and mPEG as macroinitiators. Double emulsion methods were used to prepare mPEG–PLGA NPs incorporating hydrophilic NONOate (diethylenetriamine NONOate).Results: This liposomal NP encapsulates hydrophilic diethylenetriamine NONOate (70%±4%) more effectively than other previously reported materials. The application of NO-NPs at different ratios resulted in varying NO-release profiles with no significant cytotoxicity in various cell types: normal cells (fibroblasts, human umbilical vein endothelial cells and epithelial cells) and cancer cells (C6, A549 and MCF-7). The angiogenic potential of NO-NPs was confirmed in vitro by tube formation and ex vivo through an aorta ring assay. Tubular formation increased 189.8% in NO-NP–treated groups compared with that in the control group. Rat aorta exhibited robust sprouting angiogenesis in response to NO-NPs, indicating that NO was produced by polymeric NPs in a sustained manner.Conclusion: These findings provide initial results for an angiogenesis-related drug development platform by a straightforward method with biocompatible polymers. Keywords: mPEG-PLGA nanoparticles, sprouting angiogenesis, low concentration of nitric oxide, liposomal nanoparticles, amphiphilic polymers
format	article
author	Yang C Hwang HH Jeong S Seo D Jeong Y Lee DY Lee K
author_facet	Yang C Hwang HH Jeong S Seo D Jeong Y Lee DY Lee K
author_sort	Yang C
title	Inducing angiogenesis with the controlled release of nitric oxide from biodegradable and biocompatible copolymeric nanoparticles
title_short	Inducing angiogenesis with the controlled release of nitric oxide from biodegradable and biocompatible copolymeric nanoparticles
title_full	Inducing angiogenesis with the controlled release of nitric oxide from biodegradable and biocompatible copolymeric nanoparticles
title_fullStr	Inducing angiogenesis with the controlled release of nitric oxide from biodegradable and biocompatible copolymeric nanoparticles
title_full_unstemmed	Inducing angiogenesis with the controlled release of nitric oxide from biodegradable and biocompatible copolymeric nanoparticles
title_sort	inducing angiogenesis with the controlled release of nitric oxide from biodegradable and biocompatible copolymeric nanoparticles
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/e892da029ba34f4fba983b3787417e4f
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Inducing angiogenesis with the controlled release of nitric oxide from biodegradable and biocompatible copolymeric nanoparticles

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