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Highly Thiolated Poly (Beta-Amino Ester) Nanoparticles for Acute Redox Applications

Disulfides are used extensively in reversible cross-linking because of the ease of reduction into click-reactive thiols. However, the free-radical scavenging properties upon reduction are often under-considered. The free thiols produced upon reduction of this disulfide material mimic the cellular re...

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Autores principales: Lakes, Andrew L., Puleo, David A., Hilt, J. Zach, Dziubla, Thomas D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318580/
https://www.ncbi.nlm.nih.gov/pubmed/30674856
http://dx.doi.org/10.3390/gels4040080
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author Lakes, Andrew L.
Puleo, David A.
Hilt, J. Zach
Dziubla, Thomas D.
author_facet Lakes, Andrew L.
Puleo, David A.
Hilt, J. Zach
Dziubla, Thomas D.
author_sort Lakes, Andrew L.
collection PubMed
description Disulfides are used extensively in reversible cross-linking because of the ease of reduction into click-reactive thiols. However, the free-radical scavenging properties upon reduction are often under-considered. The free thiols produced upon reduction of this disulfide material mimic the cellular reducing chemistry (glutathione) that serves as a buffer against acute oxidative stress. A nanoparticle formulation producing biologically relevant concentrations of thiols may not only provide ample chemical conjugation sites, but potentially be useful against severe acute oxidative stress exposure, such as in targeted radioprotection. In this work, we describe the synthesis and characterization of highly thiolated poly (β-amino ester) (PBAE) nanoparticles formed from the reduction of bulk disulfide cross-linked PBAE hydrogels. Degradation-tunable PBAE hydrogels were initially synthesized containing up to 26 wt % cystamine, which were reduced into soluble thiolated oligomers and formulated into nanoparticles upon single emulsion. These thiolated nanoparticles were size-stable in phosphate buffered saline consisting of up to 11.0 ± 1.1 mM (3.7 ± 0.3 mmol thiol/g, n = 3 M ± SD), which is an antioxidant concentration within the order of magnitude of cellular glutathione (1–10 mM).
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spelling pubmed-63185802019-01-17 Highly Thiolated Poly (Beta-Amino Ester) Nanoparticles for Acute Redox Applications Lakes, Andrew L. Puleo, David A. Hilt, J. Zach Dziubla, Thomas D. Gels Article Disulfides are used extensively in reversible cross-linking because of the ease of reduction into click-reactive thiols. However, the free-radical scavenging properties upon reduction are often under-considered. The free thiols produced upon reduction of this disulfide material mimic the cellular reducing chemistry (glutathione) that serves as a buffer against acute oxidative stress. A nanoparticle formulation producing biologically relevant concentrations of thiols may not only provide ample chemical conjugation sites, but potentially be useful against severe acute oxidative stress exposure, such as in targeted radioprotection. In this work, we describe the synthesis and characterization of highly thiolated poly (β-amino ester) (PBAE) nanoparticles formed from the reduction of bulk disulfide cross-linked PBAE hydrogels. Degradation-tunable PBAE hydrogels were initially synthesized containing up to 26 wt % cystamine, which were reduced into soluble thiolated oligomers and formulated into nanoparticles upon single emulsion. These thiolated nanoparticles were size-stable in phosphate buffered saline consisting of up to 11.0 ± 1.1 mM (3.7 ± 0.3 mmol thiol/g, n = 3 M ± SD), which is an antioxidant concentration within the order of magnitude of cellular glutathione (1–10 mM). MDPI 2018-10-08 /pmc/articles/PMC6318580/ /pubmed/30674856 http://dx.doi.org/10.3390/gels4040080 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lakes, Andrew L.
Puleo, David A.
Hilt, J. Zach
Dziubla, Thomas D.
Highly Thiolated Poly (Beta-Amino Ester) Nanoparticles for Acute Redox Applications
title Highly Thiolated Poly (Beta-Amino Ester) Nanoparticles for Acute Redox Applications
title_full Highly Thiolated Poly (Beta-Amino Ester) Nanoparticles for Acute Redox Applications
title_fullStr Highly Thiolated Poly (Beta-Amino Ester) Nanoparticles for Acute Redox Applications
title_full_unstemmed Highly Thiolated Poly (Beta-Amino Ester) Nanoparticles for Acute Redox Applications
title_short Highly Thiolated Poly (Beta-Amino Ester) Nanoparticles for Acute Redox Applications
title_sort highly thiolated poly (beta-amino ester) nanoparticles for acute redox applications
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318580/
https://www.ncbi.nlm.nih.gov/pubmed/30674856
http://dx.doi.org/10.3390/gels4040080
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