International Journal of Nanomedicine (Jun 2020)
Macrophage Membrane-Coated Nanoparticles Alleviate Hepatic Ischemia-Reperfusion Injury Caused by Orthotopic Liver Transplantation by Neutralizing Endotoxin
Abstract
Zhibing Ou,1,* Hua Zhong,2,* Liang Zhang,2,3 Minghua Deng,2 Wenfeng Zhang,2 Jingyuan Wang,2 Huaguo Feng,2 Jianping Gong,2 Chunmu Miao,2 Zhujun Yi2 1Department of Hepatobiliary Surgery, Chenzhou No.1 People’s Hospital, Chenzhou, Hunan 410000, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 40000, People’s Republic of China; 3Institute of Ultrasound Imaging, Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 40000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhujun Yi; Chunmu MiaoDepartment of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 40000, People’s Republic of ChinaTel +86-15803630430Email [email protected]; [email protected]: To investigate the effect and mechanism of macrophage membrane-coated nanoparticles (M-NPs) on hepatic ischemia-reperfusion injury (I/RI) caused by orthotopic liver transplantation. In addition, the advantages of TLR4+/M-NPs compared to M-NPs are discussed.Materials and Methods: We prepared biomimetic M-NPs and identified their characteristics. M-NPs were injected into an SD rat model of orthotopic liver transplantation, and the anti-inflammatory and anti-I/RI activities of M-NPs were studied in vivo and in vitro. In addition, we overexpressed macrophage membrane Toll-like receptor 4 (TLR4) in vitro and prepared TLR4+/M-NPs. Then, we assessed the characteristics and advantages of TLR4+/M-NPs.Results: The M-NPs neutralized endotoxin, inhibited the overactivation of Kupffer cells (KCs) and suppressed the secretion of inflammatory factors by inhibiting the endotoxin-mediated TLR4/MyD88/IRAK1/NF-κB signaling pathway. In an orthotopic liver transplantation model in SD rats, M-NPs showed significant therapeutic efficacy by neutralizing endotoxin and suppressing the secretion of inflammatory factors. Moreover, overexpression of TLR4 on the macrophage membrane by using a TLR4+-plasmid in vitro effectively reduced the amount of M-NPs needed to neutralize an equivalent dose of endotoxin, reducing the potential risks of NP overuse.Conclusion: This study indicates that M-NPs can effectively alleviate I/RI induced by liver transplantation.Keywords: biomimetic nanoparticle, endotoxin, Kupffer cell, liver transplantation, ischemia reperfusion injury
