State Key Laboratory of Fine Chemicals, School of Chemical Engineering, and ⊥School of Life Science and Biotechnology, Dalian University of Technology , 2 Linggong Road, 116024 Dalian, China.
Division of NanoMedicine, Department of Medicine, §California NanoSystems Institute, and ∥Department of Ecology and Evolutionary Biology, University of California , Los Angeles, California 90095, United States.
ACS Appl Mater Interfaces. 2017 Jul 5;9(26):21697-21705. doi: 10.1021/acsami.7b05817. Epub 2017 Jun 23.
Aluminum-salt-based vaccine adjuvants are prevailingly used in FDA-approved vaccines for the prevention of infectious diseases for over eighty years. Despite their safe applications, the mechanisms regarding how the material characteristics affect the interactions at nano-bio interface and immunogenicity remain unclear. Recently, studies have indicated that the activation of NLRP3 inflammasome plays a critical role in inducing adjuvant effects that are controlled by the inherent shape and hydroxyl contents of aluminum oxyhydroxide (AlOOH) nanoparticles; however, the detailed relationship between surface properties and adjuvant effects for these materials remains unknown. Thus, we engineered AlOOH nanorods (ALNRs) with controlled surface functionalization and charge to assess their effects on the activation of NLRP3 inflammasome in vitro and the potentiation of immunogenicity in vivo. It is demonstrated that NH-functionalized ALNRs exhibited higher levels of cellular uptake, lysosomal damage, oxidative stress, and NLRP3 inflammasome activation than pristine and SOH-functionalized ALNRs in cells. This structure-activity relationship also correlates with the adjuvant activity of the material using ovalbumin (OVA) in a mouse vaccination model. This study demonstrates that surface functionalization of ALNRs is critical for rational design of aluminum-based adjuvants to boost antigen-specific immune responses for more effective and long-lasting vaccination.
铝盐佐剂在过去 80 多年里被广泛应用于 FDA 批准的预防传染病疫苗中。尽管它们的应用是安全的，但关于材料特性如何影响纳米-生物界面相互作用和免疫原性的机制仍不清楚。最近的研究表明，NLRP3 炎性体的激活在诱导佐剂效应中起着关键作用，这种效应受铝氧氢氧化物（AlOOH）纳米粒子固有形状和羟基含量的控制；然而，这些材料的表面性质与佐剂效应之间的详细关系尚不清楚。因此，我们通过控制表面功能化和电荷来设计 AlOOH 纳米棒（ALNRs），以评估它们对体外 NLRP3 炎性体激活和体内免疫原性增强的影响。结果表明，与原始和 SOH 功能化的 ALNRs 相比，NH 功能化的 ALNRs 在细胞中表现出更高水平的细胞摄取、溶酶体损伤、氧化应激和 NLRP3 炎性体激活。这种结构-活性关系也与使用卵清蛋白（OVA）在小鼠疫苗接种模型中该材料的佐剂活性相关。本研究表明，ALNRs 的表面功能化对于合理设计基于铝的佐剂以增强抗原特异性免疫反应以实现更有效和持久的疫苗接种至关重要。
