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

• DOI: 10.1016/j.jconrel.2021.03.016
• Publication Date: 2021-03-18T07:39:45Z
• Authors: Eline Geervliet; Silvia Moreno; Luca Baiamonte; Richell Booijink; Susanne Boye; Peng Wang; Brigitte Voit; Albena Lederer; Dietmar Appelhans; Ruchi Bansal
• Keywords: Hepatic stellate cell; CCL4; Matrix metalloproteinase inhibitor; Hepatic fibrosis

Liver fibrosis affects millions of people worldwide and is rising vastly over the past decades. With no viable therapies available, liver transplantation only curative treatment for advanced diseased patients. Excessive accumulation aberrant extracellular matrix (ECM) proteins, mostly collagens, produced by activated hepatic stellate cells (HSCs), a hallmark fibrosis. Several studies have suggested an inverse correlation between collagen-I degrading metalloproteinase-1 (MMP-1) serum levels progression highlighting reduced MMP-1 are associated with poor disease prognosis in patients We hypothesized that delivery might potentiate collagen degradation attenuate development. In this study, we report novel approach using decorated polymersomes (MMPsomes), as surface-active vesicle-based ECM therapeutic, The storage-stable enzymatically active MMPsomes were fabricated post-loading Psomes MMP-1. extensively characterized physicochemical properties, surface localization, stability, enzymatic activity, biological effects. Dose-dependent effects MMP-1, versus empty (Psomes) + on gene protein expression collagen-I, MMP-1/TIMP-1 ratio, migration cell viability examined TGFβ-activated human HSCs. Finally, therapeutic MMPsomes, compared to evaluated vivo carbon-tetrachloride (CCl4)-induced early mouse model. exhibited favorable localization improved efficacy HSCs vitro. CCl4-induced model, inhibited intra-hepatic (ECM marker, indicating fibrosis) F4/80 (marker macrophages, inflammation) expression. conclusion, our results demonstrate innovative delivery, surface-decorated alleviating