Cited by 111Nanoparticle-Based Drug DeliveryLiver physiology and pathologyAdvanced Drug Delivery Systems

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Extracellular matrix-penetrating nanodrill micelles for liver fibrosis therapy

Fan, Qian-Qian, Zhang, Cheng-Lu, Qiao, Jian-Bin, Cui, Peng-Fei, Xing, Lei, Oh, Yu-Kyoung, Jiang, Hu-Lin·2020·Biomaterials

DOI 10.1016/j.biomaterials.2019.119616

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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.

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Authors: Fan, Q.-Q., Zhang, C.-L., Qiao, J.-B., Cui, P.-F., Xing, L., Oh, Y.-K., & Jiang, H.-L.
Affiliations: China Pharmaceutical University (CN)
Seoul National University (KR)
Corresponding author: Oh, Yu-Kyoung
Jiang, Hu-Lin
ORCID: Cui, Peng-Fei
Xing, Lei
Oh, Yu-Kyoung
Jiang, Hu-Lin
Venue: Biomaterials
Publisher: Elsevier BV
Published: 2020-02
Volume: 230
Pages: 119616
ISSN: 0142-9612 (ISSN-L)
DOI: 10.1016/j.biomaterials.2019.119616
OpenAlex: W2992864763
Cited by: 111
References: 38
Citations by year: 2026: 11 · 2025: 15 · 2024: 26 · 2023: 22 · 2022: 17 · 2021: 10 · 2020: 10
FWCI: 2.62
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Biomaterials (publishedVersion)
PubMed (publishedVersion)
Funders: National Science and Technology Major Project (2017YFA0205400)
National Natural Science Foundation of China (81773667, 81573369)
International Cooperation and Exchanges (81811540416)
First-class Project (CPU2018GY06)
Ministry of Education of China
State Administration of Foreign Experts Affairs of China (B16046)
Topics: Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Keywords: liver fibrosis, hepatic stellate cells, collagenase I, retinol, polymeric micelles, space of Disse, nilotinib, antifibrotic therapy
MeSH terms: Extracellular Matrix, Humans, Liver, Liver Cirrhosis, Micelles, Hepatic Stellate Cells

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Extracellular matrix-penetrating nanodrill micelles for liver fibrosis therapy

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