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Nano Research

Article Title

Light-triggered NO-releasing nanoparticles for treating mice with liver fibrosis

Authors

Hongxia Liang, Department of Infectious Disease and Hepatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Zhenhua Li, Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, NC 27607, USA Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, NC 27695, USA
Zhigang Ren, Department of Infectious Disease and Hepatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Qiaodi Jia, Department of Infectious Disease and Hepatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Linna Guo, The Key Lab of Chemical Biology and Organic Chemistry of Henan Province, Zhengzhou University, Zhengzhou 450001, China
Shasha Li, Department of Infectious Disease and Hepatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Hongyu Zhang, Department of Infectious Disease and Hepatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Shiqi Hu, Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, NC 27607, USA Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, NC 27695, USA
Dashuai Zhu, Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, NC 27607, USA Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, NC 27695, USA
Deliang Shen, Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Zujiang Yu, Department of Infectious Disease and Hepatology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Ke Cheng, Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, NC 27607, USA Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, NC 27695, USA

Keywords

liver fibrosis, nitric oxide (NO), hepatic stellate cells (HSC), nanoparticles, near infrared light (NIR)-controlled release

Abstract

Liver fibrosis, resulting from chronic liver damage and characterized by the accumulation of extracellular matrix (ECM) proteins, is a characteristic of most types of chronic liver diseases. The activation of hepatic stellate cells (HSC) is considered an essential pathological hallmark in liver fibrosis. Although nitric oxide (NO) can effectively induce HSC apoptosis, the systemic administration of NO is ineffective and may cause severe complications such as hypotension. To overcome this limitation, nanoparticles were designed to target HSCs and release NO locally under the exposure of near infrared light (NIR). To achieve this, upconversion nanoparticle (UCNP) cores were enveloped in mesoporous silica shells (UCNP@mSiO2), which were modified with hyaluronic acid (HA-UCNP@mSiO2) and Roussin’s black salt (RBS). HA molecules recognize and bind to CD44 proteins, which are overexpressed on activated HSCs. Under exposure to a 980-nm NIR laser, the UCNP cores convert the 980-nm wavelength into ultraviolet (UV) light, which then energizes the RBS (NO donors), resulting in an efficient release of NO inside of the HSCs. Once released, NO triggers HSC apoptosis and reverses the liver fibrosis. This targeted and controlled release method provides the theoretical and experimental basis for novel therapeutic approaches to treat hepatic fibrosis.

Graphical Abstract

Publisher

Tsinghua University Press

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