Liver-targeted delivery of TSG-6 by calcium phosphate nanoparticles for the management of liver fibrosis.

作者: Min Wang , Miao Zhang , Lianhua Fu , Jing Lin , Xinmin Zhou

DOI: 10.7150/THNO.37301

关键词:

摘要: Mesenchymal stem cells (MSCs) transplantation is a promising antifibrotic strategy but facing clinical controversies. Inspired by advances in nanomedicine, we aimed to bypass these barriers of MSCs identifying the key molecule and developing specific liver-targeting nanocarrier. Methods: Cytokines secreted were examined with serum stimulation cirrhotic patients. Immunohistochemistry, microarray, immunoblotting, quantitative real-time PCR (qRT-PCR) applied identify critical cytokine discover its role modulating effects. Biomineralization method was used prepare calcium phosphate nanoparticles (NPs). The targeting therapeutic efficiency NPs evaluated vivo imaging biochemical studies on fibrotic mice induced CCl4. Results: stimulated exhibited high-level expression Tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6). On animal study, exogenous administration TSG-6 alone can ameliorate liver fibrosis while knocked (Lv-TSG-6 MSCs) lost Further verified importance identified mechanism M2 macrophages increasing matrix metalloproteinase 12 (MMP12) expression. Additionally, found feedback loop between TSG-6, MMP12 pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), which may improve our understanding aggravating process cirrhosis mechanisms MSCs. Based findings, developed (CaP@BSA NPs) biomineralization using bovine albumin (BSA) as biotemplate. Imaging tracking drug loading showed high efficacy as-prepared CaP@BSA NPs. In study further demonstrated improved effects loaded CaP@BSA. Conclusions: major MSCs, accumulation effects, indicated translational potentials carrier for disease management.

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