Extracellular matrix-penetrating nanodrill micelles for liver fibrosis therapy.

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ID: 77471
2020
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Abstract
As hepatic stellate cells (HSCs) are essential for hepatic fibrogenesis, HSCs targeted nano-drug delivery system is a research hotspot in liver fibrosis therapy. However, the excessive deposition of fibrosis collagen (mainly collagen I) in the space of Disse associated with hepatic fibrogenesis would significantly hinder nano-formulation delivery to HSCs. Here, we have prepared a collagenase I and retinol co-decorated polymeric micelle that possess nanodrill-like and HSCs-target function based on poly-(lactic-co-glycolic)-b-poly (ethylene glycol)-maleimide (PLGA-PEG-Mal) (named CRM) for liver fibrosis therapy. Upon encountering collagen I barrier, CRM exerted a nanodrill-like function, efficiently degrading pericellular collagen I and showing greater uptake by human HSCs than other micelle formulations. Besides, CRM could realize excellent accumulation in the fibrotic liver and accurate targeting to activated HSCs in mouse hepatic fibrosis model. Moreover, CRM loaded with nilotinib (CRM/NIL), a second-generation tyrosine kinase inhibitor used in the treatment of liver fibrosis, showed optimal antifibrotic activity. This work suggests that CRM with dual function is an efficient carrier for liver fibrosis drug delivery and collagenase I decorating could be a new strategy for building more efficient HSCs targeted nano-drug delivery system.
Reference Key
fan2020extracellularbiomaterials Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Fan, Qian-Qian;Zhang, Cheng-Lu;Qiao, Jian-Bin;Cui, Peng-Fei;Xing, Lei;Oh, Yu-Kyoung;Jiang, Hu-Lin;
Journal biomaterials
Year 2020
DOI
S0142-9612(19)30715-X
URL
Keywords
hepatic stellate cell retinol extracellular matrix polymeric micelle collagenase i liver fibrosis therapy

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