Suppr超能文献

基于聚多巴胺的纳米佐剂作为一种有前途的疫苗载体,可诱导针对鲍曼不动杆菌相关性肺炎的显著免疫应答。

Polydopamine-based nano adjuvant as a promising vaccine carrier induces significant immune responses against Acinetobacter baumannii-associated pneumonia.

机构信息

Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.

Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Int J Pharm. 2024 Apr 10;654:123961. doi: 10.1016/j.ijpharm.2024.123961. Epub 2024 Mar 2.

Abstract

The objective of this study was to assess the effectiveness of polydopamine nanoparticles (PDANPs) as a delivery system for intranasal antigen administration to prevent Acinetobacter baumannii (A. baumannii)-associated pneumonia. In the in vitro phase, the conserved outer membrane protein 22 (Omp22)-encoding gene of A. baumannii was cloned, expressed, and purified, resulting in the production of recombinant Omp22 (rOmp22), which was verified using western blot. PDANPs were synthesized using dopamine monomers and loaded with rOmp22 through physical adsorption. The rOmp22-loaded PDANPs were characterized in terms of size, size distribution, zeta potential, field emission scanning electron microscopy (FESEM), loading capacity, Fourier transform infrared spectroscopy (FTIR), release profile, and cytotoxicity. In the in vivo phase, the adjuvant effect of rOmp22-loaded PDANPs was evaluated in terms of eliciting immune responses, including humoral and cytokine levels (IL-4, IL-17, and IFN-γ), as well as protection challenge. The rOmp22-loaded PDANPs were spherical with a size of 205 nm, a zeta potential of -14 mV, and a loading capacity of approximately 35.7 %. The released rOmp22 from nontoxic rOmp22-loaded PDANPs over 20 days was approximately 41.5 %, with preserved rOmp22 integrity. The IgG2a/IgG1 ratio and IFN-γ levels were significantly higher in immunized mice with rOmp22-loaded-PDANPs than in rOmp22-alum, naive Omp22, and control groups. Furthermore, rOmp22-loaded PDANPs induced effective protection against infection in the experimental challenge and showed more normal structures in the lung histopathology assay. The results of this study suggest the potential of PDANPs as a nano-adjuvant for inducing strong immune responses to combat A. baumannii.

摘要

本研究旨在评估聚多巴胺纳米粒子(PDANPs)作为鼻腔内抗原给药的递送系统,以预防鲍曼不动杆菌(A.baumannii)相关肺炎的效果。在体外阶段,我们克隆、表达和纯化了鲍曼不动杆菌的保守外膜蛋白 22(Omp22)编码基因,产生了重组 Omp22(rOmp22),并通过 Western blot 进行了验证。PDANPs 是通过多巴胺单体合成的,并通过物理吸附将 rOmp22 装载到 PDANPs 中。对载 rOmp22 的 PDANPs 的粒径、粒径分布、Zeta 电位、场发射扫描电子显微镜(FESEM)、载药量、傅里叶变换红外光谱(FTIR)、释放曲线和细胞毒性进行了表征。在体内阶段,我们评估了载 rOmp22 的 PDANPs 的佐剂效应,包括诱导免疫反应,包括体液和细胞因子水平(IL-4、IL-17 和 IFN-γ)以及保护挑战。载 rOmp22 的 PDANPs 呈球形,粒径为 205nm,Zeta 电位为-14mV,载药量约为 35.7%。在 20 天内,非毒性载 rOmp22 的 PDANPs 中释放的 rOmp22 约为 41.5%,且 rOmp22 完整性得以保留。与 rOmp22- alum、naive Omp22 和对照组相比,用载 rOmp22 的 PDANPs 免疫的小鼠的 IgG2a/IgG1 比值和 IFN-γ 水平显著升高。此外,载 rOmp22 的 PDANPs 诱导了针对实验性感染的有效保护,并在肺组织病理学检测中显示出更正常的结构。这项研究表明,PDANPs 作为一种纳米佐剂,具有诱导针对鲍曼不动杆菌的强烈免疫反应的潜力。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验