Fig. 1.

TLR and RIG-I signaling pathways intersect and can be activated by nanoparticles with encapsulated and surface-loaded pathogen-associated molecular patterns. A) Schematic of signaling pathways initiated by TLRs 1–9, and RIG-I receptors including adaptor proteins MyD88, TRIF, TRAF3, and MAVS and transcription factors NF-κB and various IRFs which regulate the transcription of proinflammatory genes. B) Left: Depiction of poly(lactic-co-glycolic acid)-polyethyleneimine nanoparticles (PLGA-PEI NPs) with encapsulated hydrophobic molecules (R848 or MPLA) and surface-loaded nucleic acids (CpG or PUUC) for adjuvant delivery during vaccination. Right: PLGA-PEI NPs with surface-loaded SARS-CoV-2 spike protein for antigen delivery during vaccination.