Matrix metalloproteinase-1 decorated polymersomes, a surface-active extracellular matrix therapeutic, potentiates collagen degradation and attenuates early liver fibrosis

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dc.contributor.authorGeervliet, Elineen_ZA
dc.contributor.authorMoreno, Silviaen_Za
dc.contributor.authorBaiamonte, Lucaen_ZA
dc.contributor.authorBooijink, Richellen_ZA
dc.contributor.authorBoye, Susanneen_ZA
dc.contributor.authorWang, Pengen_ZA
dc.contributor.authorVoit, Brigitteen_ZA
dc.contributor.authorLederer, Albenaen_ZA
dc.contributor.authorAppelhans, Dietmaren_ZA
dc.contributor.authorBansal, Ruchien_ZA
dc.date.accessioned2023-03-23T10:27:37Zen_ZA
dc.date.available2023-03-23T10:27:37Zen_ZA
dc.date.issued2021-03en_ZA
dc.descriptionCITATION: Geervliet E, Moreno S, Baiamonte L, et al. 2021. Matrix metalloproteinase-1 decorated polymersomes, a surface-active extracellular matrix therapeutic, potentiates collagen degradation and attenuates early liver fibrosis. Journal of Controlled Release : Official Journal of the Controlled Release Society. 332:594-607. doi.10.1016/j.jconrel.2021.03.016.en_ZA
dc.descriptionThe original publication is available at: europepmc.orgen_ZA
dc.description.abstractLiver fibrosis affects millions of people worldwide and is rising vastly over the past decades. With no viable therapies available, liver transplantation is the only curative treatment for advanced diseased patients. Excessive accumulation of aberrant extracellular matrix (ECM) proteins, mostly collagens, produced by activated hepatic stellate cells (HSCs), is a hallmark of liver fibrosis. Several studies have suggested an inverse correlation between collagen-I degrading matrix metalloproteinase-1 (MMP-1) serum levels and liver fibrosis progression highlighting reduced MMP-1 levels are associated with poor disease prognosis in patients with liver fibrosis. We hypothesized that delivery of MMP-1 might potentiate collagen degradation and attenuate fibrosis development. In this study, we report a novel approach for the delivery of MMP-1 using MMP-1 decorated polymersomes (MMPsomes), as a surface-active vesicle-based ECM therapeutic, for the treatment of liver fibrosis. The storagestable and enzymatically active MMPsomes were fabricated by a post-loading of Psomes with MMP-1. MMPsomes were extensively characterized for the physicochemical properties, MMP-1 surface localization, stability, enzymatic activity, and biological effects. Dose-dependent effects of MMP-1, and effects of MMPsomes versus MMP-1, empty polymersomes (Psomes) and MMP-1 + Psomes on gene and protein expression of collagen- I, MMP-1/TIMP-1 ratio, migration and cell viability were examined in TGFβ-activated human HSCs. Finally, the therapeutic effects of MMPsomes, compared to MMP-1, were evaluated in vivo in carbon-tetrachloride (CCl4)- induced early liver fibrosis mouse model. MMPsomes exhibited favorable physicochemical properties, MMP-1 surface localization and improved therapeutic efficacy in TGFβ-activated human HSCs in vitro. In CCl4-induced early liver fibrosis mouse model, MMPsomes inhibited intra-hepatic collagen-I (ECM marker, indicating early liver fibrosis) and F4/80 (marker for macrophages, indicating liver inflammation) expression. In conclusion, our results demonstrate an innovative approach of MMP-1 delivery, using surface-decorated MMPsomes, for alleviating liver fibrosis.en_ZA
dc.description.versionPublisher’s versionen_ZA
dc.format.extent14 pagesen_ZA
dc.identifier.citationGeervliet E, Moreno S, Baiamonte L, et al. 2021. Matrix metalloproteinase-1 decorated polymersomes, a surface-active extracellular matrix therapeutic, potentiates collagen degradation and attenuates early liver fibrosis. Journal of Controlled Release : Official Journal of the Controlled Release Society. 332:594-607. doi.10.1016/j.jconrel.2021.03.016.en_ZA
dc.identifier.issn0168-3659 (online)en_ZA
dc.identifier.otherdoi.10.1016/j.jconrel.2021.03.016.en_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/126705en_ZA
dc.language.isoen_ZAen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectSurface active agentsen_ZA
dc.subjectExtracellular polymeric substancesen_ZA
dc.subjectLiver -- Fibrosisen_ZA
dc.subjectMetalloproteinasesen_ZA
dc.titleMatrix metalloproteinase-1 decorated polymersomes, a surface-active extracellular matrix therapeutic, potentiates collagen degradation and attenuates early liver fibrosisen_ZA
dc.typeArticleen_ZA
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