Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus.
Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus.
复制标题
DOI：
10.1038/s41467-018-04390-7
复制
发表时间：
2018-05-17
影响因子：
16.6
通讯作者：
Sailor MJ
中科院分区：
文献类型：
--
作者：
Kim B;Pang HB;Kang J;Park JH;Ruoslahti E;Sailor MJ
小分子抗生素的不良反应和病原体耐药性的发生率正在增加。因此，人们越来越关注免疫基因疗法，以增强免疫系统对感染的反应并加速愈合。体内基因递送的主要障碍是主要摄取途径细胞内吞作用导致遗传物质的细胞外排泄和溶酶体降解。在这里，我们展示了一种绕过内吞作用并实现有效基因敲除功效的纳米系统。含有归巢肽和融合脂质体的外鞘的多孔硅纳米颗粒选择性地靶向巨噬细胞，并将寡核苷酸有效载荷直接引入胞质溶胶中。在金黄色葡萄球菌肺炎的小鼠模型中，促炎巨噬细胞标志物IRF 5的高效敲除增强了巨噬细胞的清除能力并改善了存活率。在增加细菌耐药性的背景下，靶向免疫系统以清除感染的基因治疗是一个主要目标。在这里，作者展示了一种基于硅的纳米系统，该系统在葡萄球菌肺炎的体内模型中调节巨噬细胞反应。
The incidence of adverse effects and pathogen resistance encountered with small molecule antibiotics is increasing. As such, there is mounting focus on immunogene therapy to augment the immune system’s response to infection and accelerate healing. A major obstacle to in vivo gene delivery is that the primary uptake pathway, cellular endocytosis, results in extracellular excretion and lysosomal degradation of genetic material. Here we show a nanosystem that bypasses endocytosis and achieves potent gene knockdown efficacy. Porous silicon nanoparticles containing an outer sheath of homing peptides and fusogenic liposome selectively target macrophages and directly introduce an oligonucleotide payload into the cytosol. Highly effective knockdown of the proinflammatory macrophage marker IRF5 enhances the clearance capability of macrophages and improves survival in a mouse model of Staphyloccocus aureus pneumonia. In the context of increasing bacterial antibiotic-resistance, gene therapy that targets the immune system to clear infection is a major goal. Here the authors show a silicon based nanosystem that modulates the macrophage response in an in vivo model of Staphylococcal pneumonia.
登录
查看更多内容
影响因子：
17.1
作者：
Ashley CE;Carnes EC;Epler KE;Padilla DP;Phillips GK;Castillo RE;Wilkinson DC;Wilkinson BS;Burgard CA;Kalinich RM;Townson JL;Chackerian B;Willman CL;Peabody DS;Wharton W;Brinker CJ
通讯作者：
Brinker CJ
影响因子：
9.7
作者：
Joo J;Kwon EJ;Kang J;Skalak M;Anglin EJ;Mann AP;Ruoslahti E;Bhatia SN;Sailor MJ
通讯作者：
Sailor MJ
影响因子：
10.8
作者：
Kim, Jiyoung;Santos, Olavo Amorim;Park, Ji-Ho
通讯作者：
Park, Ji-Ho
影响因子：
46.9
作者：
Gilleron, Jerome;Querbes, William;Zerial, Marino
通讯作者：
Zerial, Marino
影响因子：
2.8
作者：
Eames, H. L.;Saliba, D. G.;Udalova, I. A.
通讯作者：
Udalova, I. A.