Programmed nanoparticle-loaded microparticles for effective antigen/adjuvant delivery

Abstract

A microscale vaccine containing SiO2 nanoparticles loaded in CaCO3 microparticles was constructed using the co-precipitation method. The antigen ovalbumin (OVA) was covalently conjugated with SiO2 nanoparticles, and these nanoparticles and CpG were co-encapsulated into CaCO3 microparticles, generating a vaccine with a size of approximately 5.2μm. Scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), elemental mapping, and Fourier transform infrared (FTIR) analyses confirmed the successful preparation of the microscale vaccine; the vaccine had good storage stability without sustained antigen release, and negligible cytotoxicity to dendritic cells (DCs) and macrophages. Compared to SiO2 nanoparticles, the microscale vaccine can significantly improve antigen/adjuvant uptake. DCs internalized the entire microscale vaccine into lysosomes via macropinocytosis, and an increase in antigen endo/lysosomal escape was observed by confocal laser scanning microscopy (CLSM). Specifically, DCs pulsed with the vaccine were fully mature, expressing high levels of costimulatory molecules (CD40, CD80, and CD86), MHC II, and MHC I and secreting high levels of proinflammatory cytokines (IL-12, TNF-α, IL-1β, and IL-6). In addition, the vaccine had good in vivo biocompatibility, could protect the antigen from rapid degradation, and increased the retention time in lymph nodes. SiO2 nanoparticles-in-CaCO3 microparticles were an excellent carrier for antigen and adjuvant delivery. Hopefully, this study can provide some information on the design of microscale carriers for vaccine delivery systems.