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, La 2 O 3 boosts the highest adaptive humoral immune response, even stronger than clinically used Alum adjuvant. It could be attributed to the biotransformation of La 2 O 3 from spherical particles into urchin-like LaPO 4 , 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. Cellular internalized La 2 O 3 nanoparticles are able to transform into "sea urchin" structures in macrophages encapsulated in 3D microtissues. This unique biotransformation elicits NLRP3 inflammasome activation, bursts massive IL-1β release and results in prolonged retention of nanoparticles in 3D biological matrixes, which induce substantial adjuvant effects in animals. The IL-1β production could therefore be used to predict the immune responses of engineered nanomaterials for rapid nano-adjuvant screening. Unlabelled Image [ABSTRACT FROM AUTHOR]