Engineered MCM-48 nanoparticles as potential carriers for oral vaccine delivery.

[Display omitted] • Mesoporous silica nanoparticles (MCM-48 NPs) are engineered for oral vaccine delivery. • The MCM-48 NPs are processed to expand their pores for effective loading of large molecule antigens. • The surface of the MCM-48 NPs is grafted with polyethylene glycol for facilitated mucopenetration. • The oral administrations of the antigen-loaded engineered MCM-48 NPs show similar in vivo immunization efficacy compared to subcutaneous injections of the same dose antigens. Although convenient, oral vaccination presents challenges due to low antigen stability and limited targeting efficiency in the gastrointestinal (GI) tract. To address these issues, we specifically engineered the MCM-48 nanoparticles (NPs) as carriers for oral vaccine delivery. To accommodate large molecule antigens, the MCM-48 NPs were processed to expand their pores (MCM-48-EP NPs). To provide the muco-penetrating property and facilitate efficient delivery to M cells in the Peyer's patches, the surface of the MCM-48-EP NPs was grafted with polyethylene glycol (PEG). When loaded with a model antigen, ovalbumin (OVA), the engineered NPs retained approximately 75% of the antigens without significant release under simulated GI conditions. In vivo studies demonstrated that oral administration of the OVA-loaded engineered MCM-48 NPs elicited similar efficacy in systemic and mucosal immunization compared to subcutaneous injections of the same dose antigens. Therefore, we propose the PEG-grafted, pore-expanded MCM-48 NPs as promising carriers for oral vaccine delivery. [ABSTRACT FROM AUTHOR]