Department of Chemical Engineering and Materials Science, Wayne State University , Detroit, Michigan 48202, United States.
Department of Oncology, Wayne State University , Detroit, Michigan 48201, United States.
ACS Appl Mater Interfaces. 2017 Jul 19;9(28):23466-23475. doi: 10.1021/acsami.7b06024. Epub 2017 Jul 3.
Nanoparticles have emerged as the platform of choice to improve the efficacy and safety of subunit vaccines. A major challenge underlying the use of nanomaterials in vaccines lies in the particle designs that can efficiently target and activate the antigen-presenting cells, especially dendritic cells. Here we show a toll-like receptor 9 (TLR-9) agonist and antigen coloaded, silica nanoparticles (SiNPs) are able to accumulate in antigen presenting cells in the draining lymph nodes after injection. Vaccine loaded SiNPs led to dramatically enhanced induction of antigen-specific B and T cell responses as compared to soluble vaccines, which in turn drove a protective antitumoral immunity in a murine tumor model. Additionally, SiNP vaccines greatly reduced the production of systemic proinflammatory cytokines and completely abrogated splenomegaly, key systemic toxicities of TLR-9 agonists that limit their advances in clinical applications. Our results demonstrate that structure-optimized silica nanocarriers can be used as an effective and safe platform for targeted delivery of subunit vaccines.
纳米颗粒已成为提高亚单位疫苗疗效和安全性的首选平台。在疫苗中使用纳米材料的一个主要挑战在于可以有效靶向和激活抗原呈递细胞（尤其是树突状细胞）的颗粒设计。在这里，我们展示了一种 Toll 样受体 9（TLR-9）激动剂和抗原共负载的二氧化硅纳米颗粒（SiNPs），在注射后能够在引流淋巴结中的抗原呈递细胞中积累。与可溶性疫苗相比，负载疫苗的 SiNPs 显著增强了抗原特异性 B 和 T 细胞反应的诱导，进而在小鼠肿瘤模型中驱动了保护性抗肿瘤免疫。此外，SiNP 疫苗大大减少了全身促炎细胞因子的产生，并完全消除了脾肿大，这是 TLR-9 激动剂的关键全身毒性，限制了它们在临床应用中的进展。我们的结果表明，结构优化的二氧化硅纳米载体可用作靶向递送至亚单位疫苗的有效和安全平台。
