Gao Weiwei, Fang Ronnie H, Thamphiwatana Soracha, Luk Brian T, Li Jieming, Angsantikul Pavimol, Zhang Qiangzhe, Hu Che-Ming J, Zhang Liangfang
Department of NanoEngineering and Moores Cancer Center, University of California, San Diego , La Jolla, California 92093, United States.
Nano Lett. 2015 Feb 11;15(2):1403-9. doi: 10.1021/nl504798g. Epub 2015 Jan 26.
Synthetic nanoparticles coated with cellular membranes have been increasingly explored to harness natural cell functions toward the development of novel therapeutic strategies. Herein, we report on a unique bacterial membrane-coated nanoparticle system as a new and exciting antibacterial vaccine. Using Escherichia coli as a model pathogen, we collect bacterial outer membrane vesicles (OMVs) and successfully coat them onto small gold nanoparticles (AuNPs) with a diameter of 30 nm. The resulting bacterial membrane-coated AuNPs (BM-AuNPs) show markedly enhanced stability in biological buffer solutions. When injected subcutaneously, the BM-AuNPs induce rapid activation and maturation of dendritic cells in the lymph nodes of the vaccinated mice. In addition, vaccination with BM-AuNPs generates antibody responses that are durable and of higher avidity than those elicited by OMVs only. The BM-AuNPs also induce an elevated production of interferon gamma (INFγ) and interleukin-17 (IL-17), but not interleukin-4 (IL-4), indicating its capability of generating strong Th1 and Th17 biased cell responses against the source bacteria. These observed results demonstrate that using natural bacterial membranes to coat synthetic nanoparticles holds great promise for designing effective antibacterial vaccines.
为利用天然细胞功能开发新型治疗策略,人们越来越多地探索用细胞膜包覆的合成纳米颗粒。在此,我们报道了一种独特的细菌膜包覆纳米颗粒系统,它是一种新型且令人兴奋的抗菌疫苗。以大肠杆菌作为模式病原体,我们收集细菌外膜囊泡(OMV),并成功将它们包覆在直径为30纳米的小金纳米颗粒(AuNP)上。所得的细菌膜包覆AuNP(BM-AuNP)在生物缓冲溶液中显示出显著增强的稳定性。皮下注射时,BM-AuNP可诱导接种小鼠淋巴结中的树突状细胞快速激活和成熟。此外,用BM-AuNP进行疫苗接种所产生的抗体反应持久,且亲和力高于仅由OMV引发的反应。BM-AuNP还可诱导γ干扰素(INFγ)和白细胞介素-17(IL-17)的产生增加,但不会诱导白细胞介素-4(IL-4)的产生,这表明其能够针对源细菌产生强烈的Th1和Th17偏向性细胞反应。这些观察结果表明,利用天然细菌膜包覆合成纳米颗粒在设计有效的抗菌疫苗方面具有巨大潜力。