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Development of a Vinyl Ether-Functionalized Polyphosphoester as a Template for Multiple Postpolymerization Conjugation Chemistries and Study of Core Degradable Polymeric Nanoparticles
[Image: see text] A novel polyphosphoester (PPE) with vinyl ether side chain functionality was developed as a versatile template for postpolymerization modifications, and its degradability and biocompatibility were evaluated. An organocatalyzed ring-opening polymerization of ethylene glycol vinyl et...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296319/ https://www.ncbi.nlm.nih.gov/pubmed/25601803 http://dx.doi.org/10.1021/ma402480a |
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author | Lim, Young H. Heo, Gyu Seong Rezenom, Yohannes H. Pollack, Stephanie Raymond, Jeffery E. Elsabahy, Mahmoud Wooley, Karen L. |
author_facet | Lim, Young H. Heo, Gyu Seong Rezenom, Yohannes H. Pollack, Stephanie Raymond, Jeffery E. Elsabahy, Mahmoud Wooley, Karen L. |
author_sort | Lim, Young H. |
collection | PubMed |
description | [Image: see text] A novel polyphosphoester (PPE) with vinyl ether side chain functionality was developed as a versatile template for postpolymerization modifications, and its degradability and biocompatibility were evaluated. An organocatalyzed ring-opening polymerization of ethylene glycol vinyl ether-pendant cyclic phosphotriester monomer allowed for construction of poly(ethylene glycol vinyl ether phosphotriester) (PEVEP). This vinyl ether-functionalized PPE scaffold was coupled with hydroxyl- or thiol-containing model small molecules via three different types of conjugation chemistries—thiol–ene “click” reaction, acetalization, or thio-acetalization reaction—to afford modified polymers that accommodated either stable thio–ether or hydrolytically labile acetal or thio–acetal linkages. Amphiphilic diblock copolymers of poly(ethylene glycol) and PEVEP formed well-defined micelles with a narrow and monomodal size distribution in water, as confirmed by dynamic light scattering (DLS), transmission electron microscopy, and atomic force microscopy. The stability of the micelles and the hydrolytic degradability of the backbone and side chains of the PEVEP block segment were assessed by DLS and nuclear magnetic resonance spectroscopy ((1)H and (31)P), respectively, in aqueous buffer solutions at pH values of 5.0 and 7.4 and at temperatures of 25 and 37 °C. The hydrolytic degradation products of the PEVEP segments of the block copolymers were then identified by electrospray ionization, gas chromatography, and matrix-assisted laser desorption/ionization mass spectrometry. The parent micelles and their degradation products were found to be non-cytotoxic at concentrations up to 3 mg/mL, when evaluated with RAW 264.7 mouse macrophages and OVCAR-3 human ovarian adenocarcinoma cells. |
format | Online Article Text |
id | pubmed-4296319 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-42963192015-07-02 Development of a Vinyl Ether-Functionalized Polyphosphoester as a Template for Multiple Postpolymerization Conjugation Chemistries and Study of Core Degradable Polymeric Nanoparticles Lim, Young H. Heo, Gyu Seong Rezenom, Yohannes H. Pollack, Stephanie Raymond, Jeffery E. Elsabahy, Mahmoud Wooley, Karen L. Macromolecules [Image: see text] A novel polyphosphoester (PPE) with vinyl ether side chain functionality was developed as a versatile template for postpolymerization modifications, and its degradability and biocompatibility were evaluated. An organocatalyzed ring-opening polymerization of ethylene glycol vinyl ether-pendant cyclic phosphotriester monomer allowed for construction of poly(ethylene glycol vinyl ether phosphotriester) (PEVEP). This vinyl ether-functionalized PPE scaffold was coupled with hydroxyl- or thiol-containing model small molecules via three different types of conjugation chemistries—thiol–ene “click” reaction, acetalization, or thio-acetalization reaction—to afford modified polymers that accommodated either stable thio–ether or hydrolytically labile acetal or thio–acetal linkages. Amphiphilic diblock copolymers of poly(ethylene glycol) and PEVEP formed well-defined micelles with a narrow and monomodal size distribution in water, as confirmed by dynamic light scattering (DLS), transmission electron microscopy, and atomic force microscopy. The stability of the micelles and the hydrolytic degradability of the backbone and side chains of the PEVEP block segment were assessed by DLS and nuclear magnetic resonance spectroscopy ((1)H and (31)P), respectively, in aqueous buffer solutions at pH values of 5.0 and 7.4 and at temperatures of 25 and 37 °C. The hydrolytic degradation products of the PEVEP segments of the block copolymers were then identified by electrospray ionization, gas chromatography, and matrix-assisted laser desorption/ionization mass spectrometry. The parent micelles and their degradation products were found to be non-cytotoxic at concentrations up to 3 mg/mL, when evaluated with RAW 264.7 mouse macrophages and OVCAR-3 human ovarian adenocarcinoma cells. American Chemical Society 2014-07-02 2014-07-22 /pmc/articles/PMC4296319/ /pubmed/25601803 http://dx.doi.org/10.1021/ma402480a Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Lim, Young H. Heo, Gyu Seong Rezenom, Yohannes H. Pollack, Stephanie Raymond, Jeffery E. Elsabahy, Mahmoud Wooley, Karen L. Development of a Vinyl Ether-Functionalized Polyphosphoester as a Template for Multiple Postpolymerization Conjugation Chemistries and Study of Core Degradable Polymeric Nanoparticles |
title | Development of a Vinyl Ether-Functionalized Polyphosphoester
as a Template for Multiple Postpolymerization Conjugation Chemistries
and Study of Core Degradable Polymeric Nanoparticles |
title_full | Development of a Vinyl Ether-Functionalized Polyphosphoester
as a Template for Multiple Postpolymerization Conjugation Chemistries
and Study of Core Degradable Polymeric Nanoparticles |
title_fullStr | Development of a Vinyl Ether-Functionalized Polyphosphoester
as a Template for Multiple Postpolymerization Conjugation Chemistries
and Study of Core Degradable Polymeric Nanoparticles |
title_full_unstemmed | Development of a Vinyl Ether-Functionalized Polyphosphoester
as a Template for Multiple Postpolymerization Conjugation Chemistries
and Study of Core Degradable Polymeric Nanoparticles |
title_short | Development of a Vinyl Ether-Functionalized Polyphosphoester
as a Template for Multiple Postpolymerization Conjugation Chemistries
and Study of Core Degradable Polymeric Nanoparticles |
title_sort | development of a vinyl ether-functionalized polyphosphoester
as a template for multiple postpolymerization conjugation chemistries
and study of core degradable polymeric nanoparticles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296319/ https://www.ncbi.nlm.nih.gov/pubmed/25601803 http://dx.doi.org/10.1021/ma402480a |
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