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Macrophage Membrane-Coated Nanoparticles Alleviate Hepatic Ischemia-Reperfusion Injury Caused by Orthotopic Liver Transplantation by Neutralizing Endotoxin.
International Journal of Nanomedicine ( IF 6.6 ) Pub Date : 2020-06-11 , DOI: 10.2147/ijn.s253125 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 Yi 2
International Journal of Nanomedicine ( IF 6.6 ) Pub Date : 2020-06-11 , DOI: 10.2147/ijn.s253125 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 Yi 2
Affiliation
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
中文翻译：
巨噬细胞膜包被纳米颗粒通过中和内毒素减轻原位肝移植引起的肝缺血再灌注损伤。
目的：探讨巨噬细胞膜包覆纳米粒子（M-NPs）对原位肝移植所致肝缺血再灌注损伤（I/RI）的影响及机制。此外，还讨论了 TLR4 + /M-NPs 与 M-NPs 相比的优势。
材料和方法：我们制备了仿生 M-NPs 并确定了它们的特性。将M-NPs注射到SD大鼠原位肝移植模型中，并在体内和体外研究M-NPs的抗炎和抗I/RI活性。此外，我们在体外过表达巨噬细胞膜 Toll 样受体 4 (TLR4) 并制备了 TLR4+/M-NPs。然后，我们评估了 TLR4+/M-NPs 的特性和优势。
结果：M-NPs 中和内毒素，通过抑制内毒素介导的 TLR4/MyD88/IRAK1/NF-κB 信号通路抑制 Kupffer 细胞 (KCs) 的过度活化并抑制炎症因子的分泌。在 SD 大鼠的原位肝移植模型中，M-NPs 通过中和内毒素和抑制炎症因子的分泌显示出显着的治疗效果。此外，通过在体外使用 TLR4 + -质粒在巨噬细胞膜上过表达 TLR4有效地减少了中和等剂量内毒素所需的 M-NP 的量，从而降低了 NP 过度使用的潜在风险。
结论：本研究表明M-NPs可有效缓解肝移植引起的I/RI。
关键词：仿生纳米粒子, 内毒素, 枯否细胞, 肝移植, 缺血再灌注损伤
更新日期：2020-06-11
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
中文翻译：
巨噬细胞膜包被纳米颗粒通过中和内毒素减轻原位肝移植引起的肝缺血再灌注损伤。
目的：探讨巨噬细胞膜包覆纳米粒子（M-NPs）对原位肝移植所致肝缺血再灌注损伤（I/RI）的影响及机制。此外，还讨论了 TLR4 + /M-NPs 与 M-NPs 相比的优势。
材料和方法：我们制备了仿生 M-NPs 并确定了它们的特性。将M-NPs注射到SD大鼠原位肝移植模型中，并在体内和体外研究M-NPs的抗炎和抗I/RI活性。此外，我们在体外过表达巨噬细胞膜 Toll 样受体 4 (TLR4) 并制备了 TLR4+/M-NPs。然后，我们评估了 TLR4+/M-NPs 的特性和优势。
结果：M-NPs 中和内毒素，通过抑制内毒素介导的 TLR4/MyD88/IRAK1/NF-κB 信号通路抑制 Kupffer 细胞 (KCs) 的过度活化并抑制炎症因子的分泌。在 SD 大鼠的原位肝移植模型中，M-NPs 通过中和内毒素和抑制炎症因子的分泌显示出显着的治疗效果。此外，通过在体外使用 TLR4 + -质粒在巨噬细胞膜上过表达 TLR4有效地减少了中和等剂量内毒素所需的 M-NP 的量，从而降低了 NP 过度使用的潜在风险。
结论：本研究表明M-NPs可有效缓解肝移植引起的I/RI。
关键词：仿生纳米粒子, 内毒素, 枯否细胞, 肝移植, 缺血再灌注损伤
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