Leveraging Adrenergic Receptor Blockade for Enhanced Nonalcoholic Fatty Liver Disease Treatment via a Biomimetic Nanoplatform

Author:

Fei Bingyuan1,Zhao Yuewu2,Wang Jine2,Wen Panyue3,Li Junjie3,Tanaka Masaru3,Wang Zheng2,Li Shuo1

Affiliation:

1. Department of Gastrointestinal Colorectal Surgery. China-Japan Union Hospital of Jilin University

2. CAS Key Laboratory of Nano-Bio Interface Suzhou Institute of Nano-Tech and Nano-Bionics Chinese Academy of Sciences

3. Kyushu University

Abstract

Abstract

Nonalcoholic fatty liver disease(NAFLD) is characterized by excessive lipid accumulation, steatosis and fibrosis. Sympathetic nerves play a critical role in maintaining hepatic lipid homeostasis and regulating fibrotic progression through adrenergic receptors expressed by hepatocytes and hepatic stellate cells; however, the use of sympathetic nerve-focused strategies for the treatment of NAFLD is still in the infancy. Herein, a biomimetic nanoplatform with ROS-responsive and ROS-scavenging properties was developed for the codelivery of retinoic acid (RA) and the adrenoceptor antagonist labetalol (LA). The nanoplatform exhibited improved accumulation and sufficient drug release in the fibrotic liver, thereby achieving precise codelivery of drugs. Integration of adrenergic blockade effectively interrupted the vicious cycle of sympathetic nerves with hepatic stellate cells (HSCs) and hepatocytes, which not only combined with RA to restore HSCs to a quiescent state but also helped to reduce hepatic lipid accumulation. We demonstrated the excellent ability of the biomimetic nanoplatform to ameliorate liver inflammation, fibrosis and steatosis. Our work highlights the tremendous potential of a sympathetic nerve-focused strategy for the management of NAFLD and provides a promising nanoplatform for the treatment of NAFLD.

Publisher

Research Square Platform LLC

Reference24 articles.

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