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Programming Stem Cells for Therapeutic Angiogenesis Using Biodegradable Polymeric Nanoparticles
Published on: September 27, 2013
Inducing angiogenesis with the controlled release of nitric oxide from biodegradable and biocompatible copolymeric
Chungmo Yang1, Hae Hyun Hwang2, Soohyun Jeong1
1Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea, kangwonlee@snu.ac.kr.
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 (dieth-ylenetriamine 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.
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