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Celastrol-loaded biomimetic nanodrug ameliorates APAP-induced liver injury through modulating macrophage polarization

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单位： [1]Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China [2]Institute of Infection and Inflammation, China Three Gorges University, Yichang, China [3]Medical College, China Three Gorges University, Yichang, China [4]The People’s Hospital of China Three Gorges University, Yichang, China [5]Department of Clinical Laboratory, Affiliated Renhe Hospital of China Three Gorges University, Yichang, China [6]Tong Ji Hospital, Tongji Medical College of HUST, Wuhan, China

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Drug-induced liver injury (DILI) is a major concern in clinical treatment as well as postmarketing surveillance, showing an urgent requirement for the development of protective medications. Celastrol (Cel), a highly active natural product extracted from the roots of Tripterygium wilfordii, has a potential liver protective activity due to its antioxidant and anti-inflammatory effects. However, the further application of Cel to DILI remains a challenge because of its short half-life, low solubility, and toxic side effects. Herein, we developed a Cel-loaded biomimetic nanodrug based on erythrocyte membrane vesicles (EMV) for protecting the liver from acetaminophen (APAP)-induced liver injury. The Cel-loaded EMV (C-EMV) with lower cytotoxicity had a well-sustained release effect and exhibited excellent ability for liver accumulation under physiological and pathological conditions. By suppressing the inflammatory response of pro-inflammatory macrophage M1 polarization while stimulating anti-inflammatory macrophage M2 polarization, C-EMV could significantly alleviate the primary pathological manifestations related to liver injury, including aberrant elevation of biochemical indicators, histopathological alterations, neutrophil infiltration as well as hepatocyte DNA fragmentation. The macrophage depletion experiment further demonstrated that the protective effect of C-EMV on APAP-induced liver injury appeared to be dependent on hepatic macrophages. Therefore, C-EMV as a biomimetic nanodrug exhibits great potential for attenuating the progress of DILI, providing a new approach to protecting the liver from DILI as well as other liver inflammatory diseases through a targeted nanodelivery system. KEY MESSAGES: EMV biomimetic nanocarrier has good monodispersity and sustained-release property. EMV biomimetic nanocarrier displays excellent liver-targeting capability under physiological and pathological conditions. C-EMV biomimetic nanodrug with lower cytotoxicity regulates macrophage polarization in vitro and in vivo. C-EMV biomimetic nanodrug can significantly alleviate APAP-induced liver injury. The protective effect of C-EMV on APAP-induced liver injury is dependent on hepatic macrophages.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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出版当年[2022]版：

大类 | 2 区医学

小类 | 2 区遗传学 2 区医学：研究与实验

最新[2025]版：

大类 | 3 区医学

小类 | 3 区遗传学 3 区医学：研究与实验

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出版当年[2021]版：

Q1 GENETICS & HEREDITY Q2 MEDICINE, RESEARCH & EXPERIMENTAL

最新[2023]版：

Q1 GENETICS & HEREDITY Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子： 4.8 最新[2023版] 4.7 最新五年平均 5.606 出版当年[2021版] 6.427 出版当年五年平均 4.599 出版前一年[2020版] 4.7 出版后一年[2022版]

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第一作者单位： [1]Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China [2]Institute of Infection and Inflammation, China Three Gorges University, Yichang, China [3]Medical College, China Three Gorges University, Yichang, China [4]The People’s Hospital of China Three Gorges University, Yichang, China

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通讯机构： [1]Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, China [2]Institute of Infection and Inflammation, China Three Gorges University, Yichang, China [3]Medical College, China Three Gorges University, Yichang, China

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