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

Biomimetic nanoparticles (NPs) with virus-like shapes have been developed as novel delivery platforms and immune adjuvants to enhance immune response. However, the interaction mechanism between the nanoparticles and immune cells has been poorly understood. Hence, virus-like mesoporous silica nanoparticles (VLP) were developed and characterized with several physicochemical methods in the present study. The VLP showed an increased cellular uptake and enhanced immune response due to its biomimetic spikes on the surface compared to spherical NPs. Proteomic analysis revealed that the RIG-I-like receptor, chemokine, MAPK, Toll-like receptor signaling, 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.