Mechanism of biomimetic virus-like nanoparticles in triggering immune response elucidated by proteomics

The use of biomimetic nanoparticles (NPs) with virus-like morphology have recently attracted research interest as novel delivery platforms and immune adjuvants. However, the exact interactions between the nanoparticles and immune cells as well as the mechanism involved are not known in detail. This motivated us to develop virus-like mesoporous silica nanoparticles (VLP) to characterize their physicochemical properties, and to determine the immune pathways induced by the particles in mouse macrophages. The results showed inclusion of spikes mimicking virion structures on the surface increased cellular uptake and enhanced immune response as compared to spherical NPs. Proteomic analysis revealed that the RIG-I-like receptor signaling pathway, Chemokine signaling pathway, MAPK signaling pathway, NF-κB signaling pathway, Toll-like receptor signaling pathway, B cell receptor signaling pathway and Th1 and Th2 cell differentiation pathways were involved in regulating the immune response when macrophages interacted with VLP. When the spikes increased from 5 to 30 nm, the expression levels of immune-related proteins including TRAF6 and PIAS4 proteins enhanced. This study revealed the interaction pathways and key proteins in the activation of immune response with VLP, which may provide insights to develop novel immunotherapy for enhanced efficacy.