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

Multivalent Protein‐Loaded pH‐Stable Polymersomes: First Step toward Protein Targeted Therapeutics

“…[ 46,66 ] Using post loading, the membrane and surface of Psomes will be more favored. [ 50,65 ] Thus, the choice of loading approach will depend on the subsequent application of those protein‐loaded Psomes desired. [ 43,44,65,66 ] Furthermore, the presence of proteins in HSA‐Psomes and Avidin‐Psomes results in slightly larger membrane thicknesses compared to the reference, Empty‐Psomes (Figure 2).…”

“…[ 66 ] Moreover, matrix metalloproteinase‐1 post loaded Psomes with PEG shell outline promising benefits for the treatment of early liver fibrosis, leading to the degradation of extracellular collagen‐1. [ 50 ] Our azido‐modified, biocompatible, and pH‐responsive azido‐modified Psomes, post‐functionalized, and/or loaded with proteins/enzymes, can be further post‐functionalized with other bio(macro)molecules such as antibodies, peptides, or enzymes by click chemistry or by biotin‐avidin (derivative) interaction. The current work paves the way to the fabrication of nano‐compartments with multiple functions, while the location of active bio(macro)molecules will be selected and determined by its therapeutic action, size, and polarity.…”

“…[ 42–46 ] For most of these reactive enzymes they were mainly enclosed into the inner cavity of the polymeric vesicles during their formation process (in situ loading), [ 42–44,46 ] that is similar to formation processes of other enzymatic nanoreactors using (non‐)crosslinked Psomes. [ 14,28,47,48 ] Further own works also demonstrated i) the ability of loading and release of therapeutic hormone such as insulin, [ 49 ] ii) the loading of enzymes in Psomes through a post loading process of swollen Psomes, [ 50 ] and iii) the ability to equip the Psomes´ surface with reactive groups (azido or adamantane groups) that allow a more controlled post‐(=surface)‐functionalization. [ 51,52 ] A subsequent post‐functionalization of the Psomes surface was achieved using covalent azide‐alkyne click reaction, functionalized pH‐responsive Psomes with folate targeting antennae were also reported, [ 15 ] promoting drug release in the acidified endosomal compartment.…”

Rat bone marrow mesenchymal stem cells (BMSCs) inhibit liver fibrosis by activating GSK3β and inhibiting the Wnt3a/β-catenin pathway

“…Almost all chronic liver injury causes liver fibrosis, but the current clinical treatment of liver fibrosis is not satisfactory, and there is a lack of effective drugs, resulting in the development of cirrhosis or hepatocellular carcinoma in some patients and leading to more than 1 million deaths every year [ 19 , 20 ]. Chronic liver fibrosis greatly threatens human health, and its mechanism is complex due to an imbalance in the synthesis and degradation of extracellular matrix (EMC) during liver injury, which leads to the pathological deposition of fibrous connective tissue in liver cells [ 21 , 22 ]. Liver fibrosis can be reversed to a certain extent, and the key to reversing liver fibrosis is early and accurate diagnosis and treatment.…”

Rat bone marrow mesenchymal stem cells (BMSCs) inhibit liver fibrosis by activating GSK3β and inhibiting the Wnt3a/β-catenin pathway

“…Almost all the chronic liver injury causes liver brosis, but the current clinical treatment of liver brosis is not perfect, lack of effective treatment drugs, causing the development of cirrhosis or hepatocellular carcinoma in some patients, resulting in more than 1 million deaths every year [19,20]. Chronic liver brosis greatly threatens people's health, its formation me chanism is complex and mainly because of the imbalance of synthesis and the degradation of extracellular matrix (EMC) during the liver injury, which leads to the pathological deposition of brous connective tissue in liver cells [21,22]. Liver brosis can be reversed to a certain extent, and the key to reverse liver brosis is early and accurate diagnosis and treatment.…”