권영주 (이화여자대학교)

한빛사논문

조회399

이화여자대학교

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ACS Nano, Jan 30 2024, | https://doi.org/10.1021/acsnano.3c06107 Antioxidative Hyaluronic Acid-Bilirubin Nanomedicine Targeting Activated Hepatic Stellate Cells for Anti-Hepatic-Fibrosis Therapy

Jongyoon Shinn ¹, Seojeong Park ¹, Seonju Lee ¹, Nayoon Park¹, Seojeong Kim ¹, Seohui Hwang ¹, James J Moon ^2,3,4,5, Youngjoo Kwon ¹, Yonghyun Lee ¹

¹Department of Pharmacy, College of Pharmacy, Ewha Womans University, Seoul 03760, South Korea.

²Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.

³Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan 48109, United States.

⁴Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.

⁵Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.

J.S. and S.P. contributed equally to this work.

Corresponding Authors : Youngjoo Kwon, Yonghyun Lee

Abstract

Liver fibrosis is a life-threatening and irreversible disease. The fibrosis process is largely driven by hepatic stellate cells (HSCs), which undergo transdifferentiation from an inactivated state to an activated one during persistent liver damage. This activated state is responsible for collagen deposition in liver tissue and is accompanied by increased CD44 expression on the surfaces of HSCs and amplified intracellular oxidative stress, which contributes to the fibrosis process. To address this problem, we have developed a strategy that combines CD44-targeting of activated HSCs with an antioxidative approach. We developed hyaluronic acid-bilirubin nanoparticles (HABNs), composed of endogenous bilirubin, an antioxidant and anti-inflammatory bile acid, and hyaluronic acid, an endogenous CD44-targeting glycosaminoglycan biopolymer. Our findings demonstrate that intravenously administered HABNs effectively targeted the liver, particularly activated HSCs, in fibrotic mice with choline-deficient l-amino acid-defined high-fat diet (CD-HFD)-induced nonalcoholic steatohepatitis (NASH). HABNs were able to inhibit HSC activation and proliferation and collagen production. Furthermore, in a murine CD-HFD-induced NASH fibrosis model, intravenously administered HABNs showed potent fibrotic modulation activity. Our study suggests that HABNs have the potential to serve as a targeted anti-hepatic-fibrosis therapy by modulating activated HSCs via CD44-targeting and antioxidant strategies. This strategy could also be applied to various ROS-related diseases in which CD44-overexpressing cells play a pivotal role.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-01-31)
연구진국내(교신)+국외 연구진
분야 의약학 > 약학

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