<p>Macrophage Membrane-Coated Nanoparticles Alleviate Hepatic Ischemia-Reperfusion Injury Caused by Orthotopic Liver Transplantation by Neutralizing Endotoxin</p>
Zhi-bing Ou, Hua Zhong, Liang Zhang, Minghua Deng, Wenfeng Zhang, Jingyuan Wang, Huaguo Feng, Jianping Gong, Chunmu Miao, Zhujun Yi
Abstract
Purpose: 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