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Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections
Nanoscale Horizons ( IF 8.0 ) Pub Date : 2021-2-9 , DOI: 10.1039/d0nh00624f Byungji Kim 1 , Qinglin Yang , Leslie W Chan , Sangeeta N Bhatia , Erkki Ruoslahti , Michael J Sailor
Nanoscale Horizons ( IF 8.0 ) Pub Date : 2021-2-9 , DOI: 10.1039/d0nh00624f Byungji Kim 1 , Qinglin Yang , Leslie W Chan , Sangeeta N Bhatia , Erkki Ruoslahti , Michael J Sailor
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Bacterial infections are re-emerging as substantial threats to global health due to the limited selection of antibiotics that are capable of overcoming antibiotic-resistant strains. By deterring such mutations whilst minimizing the need to develop new pathogen-specific antibiotics, immunotherapy offers a broad-spectrum therapeutic solution against bacterial infections. In particular, pathology resulting from excessive immune response (i.e. fibrosis, necrosis, exudation, breath impediment) contributes significantly to negative disease outcome. Herein, we present a nanoparticle that is targeted to activated macrophages and loaded with siRNA against the Irf5 gene. This formulation is able to induce >80% gene silencing in activated macrophages in vivo, and it inhibits the excessive inflammatory response, generating a significantly improved therapeutic outcome in mouse models of bacterial infection. The versatility of the approach is demonstrated using mice with antibiotic-resistant Gram-positive (methicillin-resistant Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) muscle and lung infections, respectively. Effective depletion of the Irf5 gene in macrophages is found to significantly improve the therapeutic outcome of infected mice, regardless of the bacteria strain and type.
中文翻译：
融合多孔硅纳米颗粒作为针对细菌感染的广谱免疫疗法
由于能够克服抗生素耐药菌株的抗生素选择有限，细菌感染重新成为全球健康的重大威胁。通过阻止此类突变，同时最大限度地减少开发新的病原体特异性抗生素的需求，免疫疗法提供了针对细菌感染的广谱治疗解决方案。特别是，过度免疫反应（即纤维化、坏死、渗出、呼吸障碍）引起的病理学对负面疾病结果有显着贡献。在此，我们提出了一种纳米颗粒，该纳米颗粒靶向激活的巨噬细胞，并装载有针对Irf5基因的 siRNA。该制剂能够在体内诱导活化的巨噬细胞中>80%的基因沉默，并抑制过度的炎症反应，从而在细菌感染的小鼠模型中产生显着改善的治疗结果。该方法的多功能性通过分别使用具有抗生素耐药性革兰氏阳性（耐甲氧西林金黄色葡萄球菌）和革兰氏阴性（铜绿假单胞菌）肌肉和肺部感染的小鼠来证明。研究发现，无论细菌菌株和类型如何，有效清除巨噬细胞中的Irf5基因都可以显着改善受感染小鼠的治疗结果。
更新日期：2021-02-18
中文翻译：
融合多孔硅纳米颗粒作为针对细菌感染的广谱免疫疗法
由于能够克服抗生素耐药菌株的抗生素选择有限，细菌感染重新成为全球健康的重大威胁。通过阻止此类突变，同时最大限度地减少开发新的病原体特异性抗生素的需求，免疫疗法提供了针对细菌感染的广谱治疗解决方案。特别是，过度免疫反应（即纤维化、坏死、渗出、呼吸障碍）引起的病理学对负面疾病结果有显着贡献。在此，我们提出了一种纳米颗粒，该纳米颗粒靶向激活的巨噬细胞，并装载有针对Irf5基因的 siRNA。该制剂能够在体内诱导活化的巨噬细胞中>80%的基因沉默，并抑制过度的炎症反应，从而在细菌感染的小鼠模型中产生显着改善的治疗结果。该方法的多功能性通过分别使用具有抗生素耐药性革兰氏阳性（耐甲氧西林金黄色葡萄球菌）和革兰氏阴性（铜绿假单胞菌）肌肉和肺部感染的小鼠来证明。研究发现，无论细菌菌株和类型如何，有效清除巨噬细胞中的Irf5基因都可以显着改善受感染小鼠的治疗结果。
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