Manganese Carbonyl-Loaded Hollow Mesoporous Silica Nanoparticles Coated with Neutrophil Membranes for Acute Kidney Injury Therapy
Manganese Carbonyl-Loaded Hollow Mesoporous Silica Nanoparticles Coated with Neutrophil Membranes for Acute Kidney Injury Therapy
复制标题
DOI：
10.1021/acsanm.2c00071
复制
发表时间：
2022-02
影响因子：
5.9
通讯作者：
Guihua Zhou;Wencong Zhao;Chunyu Zhang;Xueyun Gao;Q. Cheng;Fuping Gao
中科院分区：
文献类型：
--
作者：
Guihua Zhou;Wencong Zhao;Chunyu Zhang;Xueyun Gao;Q. Cheng;Fuping Gao
急性肾损伤（阿基）在住院患者中的发生率很高，但临床上缺乏有效的治疗方法。其发病机制与肾小管周围毛细血管灌注不足、活性氧自由基（ROS）产生和炎性细胞浸润有关。内源性一氧化碳（CO）可通过舒张血管、抗炎和减轻氧化应激损伤来保护细胞或器官。但直接外源性CO补充难以控制确切剂量，且过量CO毒性明显，难以在临床治疗中应用。在这项研究中，我们通过将羰基锰（MnCO）负载到中空介孔硅纳米颗粒（hMSN）上来构建H2 O2响应性纳米药物，所述中空介孔硅纳米颗粒（hMSN）涂覆有中性粒细胞膜，并在膜表面插入磷脂酰丝氨酸（PS）（MnCO@hMSN@NM-PS）。MnCO@hMSN@NM-PS通过中性粒细胞膜对炎症部位的仿生趋化作用以及PS与受损肾小管上皮细胞中过表达的肾损伤分子-1（KIM-1）的主动结合而定位于阿基的肾小管中。MnCO@hMSN@NM-PS对体外培养的肾小管细胞氧化损伤和体内甘油诱导的AKI均有较好的保护作用。MnCO@hMSN@NM-PS为阿基的治疗带来了希望。
Acute kidney injury (AKI) has a very high incidence in hospitalized patients, but it lacks effective therapy clinically. Its pathogenesis is associated with capillary hypoperfusion around renal tubules, production of reactive oxygen free radicals (ROS), and infiltration of inflammatory cells. Endogenous carbon monoxide (CO) can protect cells or organs by vasodilation, anti-inflammation, and reducing oxidative stress injury. However, direct exogenous CO supplementation is difficult to control the exact dose, and excessive CO has obvious toxicity, which is difficult to be applied in clinical treatment. In this study, we constructed H2O2-responsive nanomedicine for CO therapy of AKI by loading manganese carbonyl (MnCO) onto the hollow mesoporous silicon nanoparticles (hMSN), which were coated with a neutrophil membrane with the insertion of phosphatidylserine (PS) into the membrane surface (MnCO@hMSN@NM-PS). MnCO@hMSN@NM-PS was located in the renal tubules of AKI through the biomimetic chemotaxis of the neutrophil membrane to the inflammation site and the active binding of PS to kidney injury molecule-1 (KIM-1), which was overexpressed in damaged renal tubular epithelial cells. MnCO@hMSN@NM-PS had a good protective effect on oxidative damage of renal tubular cellsin vitroand glycerol-induced AKIin vivo. MnCO@hMSN@NM-PS offers hope for the treatment of AKI.