Products Cited in Publications Worldwide Triggered and tuneable H2S release from star polymers with acyl-protected perthiol groups in the core

Triggered and tuneable H2S release from star polymers with acyl-protected perthiol groups in the core

Nazemi, Katayoun; Ercole, Francesca; Nay, Kevin; Do, An Huong; Rowe, Matthew C; Dao, Nam V; Whittaker, Michael R; Quinn, John F

DOI:

Abstract

Hydrogen sulfide (H2S) is a signalling molecule with activity across a wide range of biological functions. As a result, H2S has attracted significant attention due to its potential therapeutic application in a variety of pathologies, and new delivery systems are of considerable interest. To this end, H2S-releasing polymeric nanoparticles (i.e., core-crosslinked star polymers) were prepared via a two-step modification, utilising pentafluorophenyl acrylate (PFPA) moieties installed in the star polymer cores as a reactive platform. Specifically, PFPA moieties were substituted with 2-(2-pyridyl)ethylamine to provide pyridyl-disulfide functionality in the star polymer core, and a subsequent thiol-exchange reaction with thiobenzoic acid was employed to convert these to H2S-releasing acyl-protected perthiol groups. These acyl-protected perthiol moieties serve as triggerable agents capable of controlled H2S release when exposed to biological thiols. The H2S release profile of star polymers with three different sizes (50K to 100K (Da)) was investigated upon exposure to two triggers of varying molecular size: L-cysteine and glutathione, and the release profile of H2S from star polymers in HEK 293 cells were found to be dependent on the star size. Notably, increasing star size resulted in progressively delayed release. Additionally, the star polymers exhibited the potential to attenuate oxidative stress associated with application of an exogenous oxidant (200 µM H2O2). When comparing the effectiveness of H2S-releasing star polymers in mitigating oxidative stress with TEMPO-functional star polymer (a material with established selective scavenging of reactive oxygen species in mitochondria), it was evident that, at higher concentrations, the TEMPO-star polymer was toxic to the cells. In contrast, the acyl-protected perthiol emerged as a well-tolerated and effective ROS scavenger. These results demonstrate that acyl-protected perthiol-functionalised star polymers are an effective delivery system for H2S, and can attenuate ROS levels when applied at an appropriate concentration.

Keywords

Star polymers ; Hydrogen sulfide ; Acyl-protected perthiol ; TEMPO ; Reactive oxygen species

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