Back to Journals » International Journal of Nanomedicine » Volume 13

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

Authors Yang C, Hwang HH, Jeong S, Seo D, Jeong Y, Lee DY, Lee K

Received 25 May 2018

Accepted for publication 9 August 2018

Published 16 October 2018 Volume 2018:13 Pages 6517—6530


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Thomas Webster

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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]