Development of a shape-controlled H 2 S delivery system using epoxide-functional nanoparticles

Sul Hwa Yu, Lars Esser, Song Yang Khor, Danielle Senyschyn, Nicholas A. Veldhuis, Michael R. Whittaker, Francesca Ercole, Thomas P. Davis, John F. Quinn

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Hydrogen sulfide (H 2 S), an endogenous modulator of signaling processes, has potential as a therapeutic drug or in combination drug therapies. Due to its broad biological impacts and malodorous nature, there is considerable interest in vehicles capable of delivering H 2 S in a controlled manner. Herein, we report postpolymerization modification of polymers incorporating glycidyl methacrylate (GMA) units to form thiol-triggered macromolecular H 2 S donors. By combining this approach with polymerization-induced self-assembly, this methodology allows the facile preparation of polymeric nanoparticulate donors with either spherical or worm-like morphology. The thiol-reactive epoxide functional groups in poly(GMA) were chemically transformed into acyl-protected perthiol groups using a three-step procedure throughout which both morphologies remained intact. The H 2 S releasing properties were subsequently studied, with both spherical and worm-like nanoparticulate donors shown to successfully release H 2 S in the presence of the model thiol, l-cysteine. In addition, the donor polymers were shown to effectively increase H 2 S inside cells, upon exposure to biologically relevant endogenous thiol levels.

Original languageEnglish
Number of pages12
JournalJournal of Polymer Science, Part A: Polymer Chemistry
DOIs
Publication statusAccepted/In press - 23 Apr 2019

Keywords

  • acyl-protected perthiol groups
  • block copolymers
  • drug delivery systems
  • hydrogen sulfide
  • nanoparticles
  • nanoparticulate donor
  • polymerization-induced self-assembly
  • postpolymerization modification
  • spherical and worm-like nanoparticulate donors
  • thiol

Cite this

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title = "Development of a shape-controlled H 2 S delivery system using epoxide-functional nanoparticles",
abstract = "Hydrogen sulfide (H 2 S), an endogenous modulator of signaling processes, has potential as a therapeutic drug or in combination drug therapies. Due to its broad biological impacts and malodorous nature, there is considerable interest in vehicles capable of delivering H 2 S in a controlled manner. Herein, we report postpolymerization modification of polymers incorporating glycidyl methacrylate (GMA) units to form thiol-triggered macromolecular H 2 S donors. By combining this approach with polymerization-induced self-assembly, this methodology allows the facile preparation of polymeric nanoparticulate donors with either spherical or worm-like morphology. The thiol-reactive epoxide functional groups in poly(GMA) were chemically transformed into acyl-protected perthiol groups using a three-step procedure throughout which both morphologies remained intact. The H 2 S releasing properties were subsequently studied, with both spherical and worm-like nanoparticulate donors shown to successfully release H 2 S in the presence of the model thiol, l-cysteine. In addition, the donor polymers were shown to effectively increase H 2 S inside cells, upon exposure to biologically relevant endogenous thiol levels.",
keywords = "acyl-protected perthiol groups, block copolymers, drug delivery systems, hydrogen sulfide, nanoparticles, nanoparticulate donor, polymerization-induced self-assembly, postpolymerization modification, spherical and worm-like nanoparticulate donors, thiol",
author = "Yu, {Sul Hwa} and Lars Esser and Khor, {Song Yang} and Danielle Senyschyn and Veldhuis, {Nicholas A.} and Whittaker, {Michael R.} and Francesca Ercole and Davis, {Thomas P.} and Quinn, {John F.}",
year = "2019",
month = "4",
day = "23",
doi = "10.1002/pola.29382",
language = "English",
journal = "Journal of Polymer Science, Part A: Polymer Chemistry",
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publisher = "Wiley-Blackwell",

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T1 - Development of a shape-controlled H 2 S delivery system using epoxide-functional nanoparticles

AU - Yu, Sul Hwa

AU - Esser, Lars

AU - Khor, Song Yang

AU - Senyschyn, Danielle

AU - Veldhuis, Nicholas A.

AU - Whittaker, Michael R.

AU - Ercole, Francesca

AU - Davis, Thomas P.

AU - Quinn, John F.

PY - 2019/4/23

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N2 - Hydrogen sulfide (H 2 S), an endogenous modulator of signaling processes, has potential as a therapeutic drug or in combination drug therapies. Due to its broad biological impacts and malodorous nature, there is considerable interest in vehicles capable of delivering H 2 S in a controlled manner. Herein, we report postpolymerization modification of polymers incorporating glycidyl methacrylate (GMA) units to form thiol-triggered macromolecular H 2 S donors. By combining this approach with polymerization-induced self-assembly, this methodology allows the facile preparation of polymeric nanoparticulate donors with either spherical or worm-like morphology. The thiol-reactive epoxide functional groups in poly(GMA) were chemically transformed into acyl-protected perthiol groups using a three-step procedure throughout which both morphologies remained intact. The H 2 S releasing properties were subsequently studied, with both spherical and worm-like nanoparticulate donors shown to successfully release H 2 S in the presence of the model thiol, l-cysteine. In addition, the donor polymers were shown to effectively increase H 2 S inside cells, upon exposure to biologically relevant endogenous thiol levels.

AB - Hydrogen sulfide (H 2 S), an endogenous modulator of signaling processes, has potential as a therapeutic drug or in combination drug therapies. Due to its broad biological impacts and malodorous nature, there is considerable interest in vehicles capable of delivering H 2 S in a controlled manner. Herein, we report postpolymerization modification of polymers incorporating glycidyl methacrylate (GMA) units to form thiol-triggered macromolecular H 2 S donors. By combining this approach with polymerization-induced self-assembly, this methodology allows the facile preparation of polymeric nanoparticulate donors with either spherical or worm-like morphology. The thiol-reactive epoxide functional groups in poly(GMA) were chemically transformed into acyl-protected perthiol groups using a three-step procedure throughout which both morphologies remained intact. The H 2 S releasing properties were subsequently studied, with both spherical and worm-like nanoparticulate donors shown to successfully release H 2 S in the presence of the model thiol, l-cysteine. In addition, the donor polymers were shown to effectively increase H 2 S inside cells, upon exposure to biologically relevant endogenous thiol levels.

KW - acyl-protected perthiol groups

KW - block copolymers

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KW - hydrogen sulfide

KW - nanoparticles

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KW - polymerization-induced self-assembly

KW - postpolymerization modification

KW - spherical and worm-like nanoparticulate donors

KW - thiol

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