期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 293, 期 29, 页码 11310-11324出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.RA118.002550
关键词
amyloid; albumin; nanotechnology; drug delivery; drug delivery system; antigen; antigen delivery; nanosheet; ovalbumin
资金
- University Grants Commission, Government of India
Amyloids are associated with many neurodegenerative diseases, motivating investigations into their structure and function. Although not linked to a specific disease, albumins have been reported to form many structural aggregates. We were interested in investigating host immune responses to amyloid fibrils assembled from the model protein ovalbumin. Surprisingly, upon subjecting ovalbumin to standard denaturing conditions, we encountered giant protein nanosheets harboring amyloid-like features and hypothesized that these nanosheets might have potential in clinical or therapeutic applications. We found that the nanosheets, without the administration of any additional adjuvant, evoked a strong antibody response in mice that was higher than that observed for native ovalbumin. This suggests that amyloid nanosheets have a self-adjuvanting property. The nanosheet-induced immune response was helper T cell 2 (Th2) biased and negligibly inflammatory. While testing whether the nanosheets might form depots for the sustained release of precursor proteins, we did observe release of ovalbumin that mimicked the conformation of native protein. Moreover, the nanosheets could load the anticancer drug doxorubicin and release it in a slow and sustained manner. Taken together, our results suggest that amyloid nanosheets should be further investigated as either an antigen delivery vehicle or a multifunctional antigen and drug co-delivery system, with potential applications in simultaneous immunotherapy and chemotherapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据