Ceria Nanoparticles Meet Hepatic Ischemia-Reperfusion Injury: The Perfect Imperfection
Ceria Nanoparticles Meet Hepatic Ischemia-Reperfusion Injury: The Perfect Imperfection
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二氧化铈纳米颗粒应对肝缺血再灌注损伤：完美的缺陷
DOI：
10.1002/adma.201902956
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发表时间：
2019-08-16
影响因子：
29.4
通讯作者：
Cai, Weibo
中科院分区：
文献类型：
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作者：
Ni, Dalong;Wei, Hao;Cai, Weibo
在翻译纳米药物时，单核巨噬细胞系统(MPS，如肝、脾)经常被纳米研究人员视为“黑匣子”。通常，大多数注射的纳米材料被MPS隔离，阻止它们传递到所需的疾病区域。在这里，这种缺陷是通过应用具有优先肝脏摄取的纳米抗氧化剂来直接预防肝脏缺血再灌注损伤(IRI)，这是一种与活性氧(ROS)相关的疾病。选择纳米CeO_2(NPs)作为具有代表性的纳米抗氧化剂，并对其预防IRI的具体机理进行了研究。研究发现，纳米CeO2通过清除ROS，抑制Kupffer细胞和单核/巨噬细胞的活化，有效地缓解了肝脏IRI的临床症状。然后，释放的促炎细胞因子显著减少，中性粒细胞的募集和渗透减少，从而抑制随后涉及肝脏的炎症反应。纳米抗氧化剂对活体动物肝脏IRI的保护作用及其揭示的机制提示其在临床治疗肝脏IRI方面的应用前景。
The mononuclear phagocyte system (MPS, e.g., liver, spleen) is often treated as a "blackbox" by nanoresearchers in translating nanomedicines. Often, most of the injected nanomaterials are sequestered by the MPS, preventing their delivery to the desired disease areas. Here, this imperfection is exploited by applying nano-antioxidants with preferential liver uptake to directly prevent hepatic ischemia-reperfusion injury (IRI), which is a reactive oxygen species (ROS)-related disease. Ceria nanoparticles (NPs) are selected as a representative nano-antioxidant and the detailed mechanism of preventing IRI is investigated. It is found that ceria NPs effectively alleviate the clinical symptoms of hepatic IRI by scavenging ROS, inhibiting activation of Kupffer cells and monocyte/macrophage cells. The released pro-inflammatory cytokines are then significantly reduced and the recruitment and infiltration of neutrophils are minimized, which suppress subsequent inflammatory reaction involved in the liver. The protective effect of nano-antioxidants against hepatic IRI in living animals and the revealed mechanism herein suggests their future use for the treatment of hepatic IRI in the clinic.