Background: Nanocarriers could deliver significantly higher amounts of antigen to antigen-presenting cells (APCs), which have great potential to stimulate humoral and cellular response in cancer immunotherapy. Thereafter, silica solid nanosphere (SiO₂) was prepared, and a model antigen (ovalbumin, OVA) was covalently conjugated on the surface of SiO₂ to form nanovaccine (OVA@SiO₂). And the application of OVA@SiO₂ for cancer immunotherapy was evaluated.
Materials and Methods: SiO₂ solid nanosphere was prepared by the Stöber method, then successively aminated by aminopropyltriethoxysilane and activated with glutaraldehyde. OVA was covalently conjugated on the surface of activated SiO₂ to obtain nanovaccine (OVA@SiO₂). Dynamic light scattering, scanning electron microscope, and transmission electron microscope were conducted to identify the size distribution, zeta potential and morphology of OVA@SiO₂. The OVA loading capacity was investigated by varying glutaraldehyde concentration. The biocompatibility of OVA@SiO₂ to DC2.4 and RAW246.7 cells was evaluated by a Cell Counting Kit-8 assay. The uptake of OVA@SiO₂ by DC2.4 and its internalization pathway were evaluated in the absence or presence of different inhibitors. The activation and maturation of bone marrow-derived DC cells by OVA@SiO₂ were also investigated. Finally, the in vivo transport of OVA@SiO₂ and its toxicity to organs were appraised.
Results: All results indicated the successful covalent conjugation of OVA on the surface of SiO₂. The as-prepared OVA@SiO₂ possessed high antigen loading capacity, which had good biocompatibility to APCs and major organs. Besides, OVA@SiO₂ facilitated antigen uptake by DC2.4 cells and its cytosolic release. Noteworthily, OVA@SiO₂ significantly promoted the maturation of dendritic cells and up-regulation of cytokine secretion by co-administration of adjuvant CpG-ODN.
Conclusion: The as-prepared SiO₂ shows promising potential for use as an antigen delivery carrier.
Keywords: antigen delivery, silica solid sphere, nanovaccine, cancer immunotherapy