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 (SiO) was prepared, and a model antigen (ovalbumin, OVA) was covalently conjugated on the surface of SiO to form nanovaccine (OVA@SiO). And the application of OVA@SiO for cancer immunotherapy was evaluated. MATERIALS AND METHODS: SiO 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 SiO to obtain nanovaccine (OVA@SiO). Dynamic light scattering, scanning electron microscope, and transmission electron microscope were conducted to identify the size distribution, zeta potential and morphology of OVA@SiO. The OVA loading capacity was investigated by varying glutaraldehyde concentration. The biocompatibility of OVA@SiO to DC2.4 and RAW246.7 cells was evaluated by a Cell Counting Kit-8 assay. The uptake of OVA@SiO 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@SiO were also investigated. Finally, the in vivo transport of OVA@SiO and its toxicity to organs were appraised. RESULTS: All results indicated the successful covalent conjugation of OVA on the surface of SiO. The as-prepared OVA@SiO possessed high antigen loading capacity, which had good biocompatibility to APCs and major organs. Besides, OVA@SiO facilitated antigen uptake by DC2.4 cells and its cytosolic release. Noteworthily, OVA@SiO significantly promoted the maturation of dendritic cells and up-regulation of cytokine secretion by co-administration of adjuvant CpG-ODN. CONCLUSION: The as-prepared SiO shows promising potential for use as an antigen delivery carrier.