Exploring the interactions between engineered nanomaterials and immune cells at 3D nano-bio interfaces to discover potent nano-adjuvants

Engineered nanomaterials (ENMs) as adjuvants can potentiate the adaptive immune responses to antigens by activating immune cells in three dimensional (3D) matrixes of tissues. However, few reports explored the interactions of nano-adjuvants and immune cells at 3D nano-bio interfaces. Herein we designed an alginate-calcium microsphere of macrophage cells to explore the interactions. By an extensive comparison of ENM-induced cytokines in 2D and 3D cultured cells, IL-1β released in 3D microspheres was found to be a predictive biomarker to assess ENM-induced immune responses in vivo. Among nine representative ENMs, La2O3 boosts the highest adaptive humoral immune response, even stronger than clinically used Alum adjuvant. It could be attributed to the biotransformation of La2O3 from spherical particles into urchin-like LaPO4, resulting in strong biopersistence and NLRP3 inflammasome activation. These findings could be potentially used for the high throughput screening of nano-adjuvants from increasingly invented ENMs to speed up their clinical uses.