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Hydrogen sulfide-releasing micelles for promoting angiogenesis.

ABSTRACT: Hydrogen sulfide (H₂S), an important gaseous signalling molecule in the human body, has been shown to be involved in many physiological processes such as angiogenesis. Since the biological activities of H₂S are known to be significantly affected by the dose and exposure duration, the development of H₂S delivery systems that enable control of H₂S release is critical for exploring its therapeutic potential. Here, we prepared polymeric micelles with different H₂S release profiles, which were prepared from amphiphilic block copolymers consisting of a hydrophilic poly(N-acryloyl morpholine) segment and a hydrophobic segment containing H₂S-releasing anethole dithiolethione (ADT) groups. The thermodynamic stability of the micelles was modulated by altering the ADT content of the polymers. The micelles with higher thermodynamic stability showed significantly slower H₂S release. Furthermore, the sustained H₂S release from the micelles enhanced migration and tube formation in human umbilical vein cells (HUVECs) and induced vascularlization in the in ovo chick chorioallantoic membrane (CAM) assay.

SUBMITTER: Chen JJY

PROVIDER: S-EPMC8009299 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Hydrogen sulfide-releasing micelles for promoting angiogenesis.

Chen Jerry J Y JJY van der Vlies A J AJ Hasegawa U U

Polymer chemistry 20200616

Hydrogen sulfide (H2S), an important gaseous signalling molecule in the human body, has been shown to be involved in many physiological processes such as angiogenesis. Since the biological activities of H2S are known to be significantly affected by the dose and exposure duration, the development of H2S delivery systems that enable control of H2S release is critical for exploring its therapeutic potential. Here, we prepared polymeric micelles with diffe ...[more]

PMID: 33796157

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Project description:By electrospinning of polycaprolactone (PCL) solutions containing N-(benzoylthio)benzamide (NSHD1), a H2S donor, fibrous scaffolds with hydrogen sulfide (H2S) releasing capability (H2S-fibers) are fabricated. The resultant microfibers are capable of releasing H2S upon immersion in aqueous solution containing biological thiols under physiological conditions. The H2S release peaks of H2S-fibers appeared at 2-4h, while the peak of donor alone showed at 45 min. H2S release half-lives of H2S-fibers were 10-20 times longer than that of donor alone. Furthermore, H2S-fibers can protect cells from H2O2 induced oxidative damage by significantly decreasing the production of intracellular reactive oxygen species (ROS). Finally, we investigated the H2S-fibers application as a wound dressing in vitro. Given that H2S has a broad range of physiological functions, H2S-fibers hold great potential for various biomedical applications.Statement of significanceHydrogen sulfide, as a gaseous messenger, plays a crucial role in many physiological and pathological conditions. Recent studies about functions of H2S suggests H2S-based therapy could be promising therapeutic strategy for many diseases, such as cardiovascular disease, arthritis, and inflammatory bowel disease. Although many H2S donors have been developed and applied for biomedical studies, most of H2S donors have the shortage that the H2S release is either too fast or uncontrollable, which poorly mimic the biological generation of H2S. By simply combining electrospinning technique with our designed biological thiols activated H2S donor, NSHD1, we fabricated H2S releasing microfibers (H2S-fibers). This H2S-fibers significantly prolonged the releasing time compared to H2S donor alone. By adjusting the electrospinning parameters, tunable releasing profiles can be achieved. Moreover, the H2S fibers can protect cardiac myoblasts H9c2 and fibroblast NIH 3T3 from oxidative damage and support their proliferation as cellular scaffolds. To our knowledge, this is the first report of electrospun fibers with H2S releasing capacity. We anticipate this H2S-releasing scaffold will have great potential for biomedical applications.

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Hydrogen sulfide-releasing micelles for promoting angiogenesis.

Publications

Hydrogen sulfide-releasing micelles for promoting angiogenesis.

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