<p>Antigen-Conjugated Silica Solid Sphere as Nanovaccine for Cancer Immunotherapy</p>

Abstract

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 2 ) was prepared, and a model antigen (ovalbumin, OVA) was covalently conjugated on the surface of SiO 2 to form nanovaccine ( [email protected] 2 ). And the application of [email protected] 2 for cancer immunotherapy was evaluated. Materials and Methods: SiO 2 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 2 to obtain nanovaccine ( [email protected] 2 ). Dynamic light scattering, scanning electron microscope, and transmission electron microscope were conducted to identify the size distribution, zeta potential and morphology of [email protected] 2 . The OVA loading capacity was investigated by varying glutaraldehyde concentration. The biocompatibility of [email protected] 2 to DC2.4 and RAW246.7 cells was evaluated by a Cell Counting Kit-8 assay. The uptake of [email protected] 2 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 [email protected] 2 were also investigated. Finally, the in vivo transport of [email protected] 2 and its toxicity to organs were appraised. Results: All results indicated the successful covalent conjugation of OVA on the surface of SiO 2 . The as-prepared [email protected] 2 possessed high antigen loading capacity, which had good biocompatibility to APCs and major organs. Besides, [email protected] 2 facilitated antigen uptake by DC2.4 cells and its cytosolic release. Noteworthily, [email protected] 2 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 2 shows promising potential for use as an antigen delivery carrier. Keywords: antigen delivery, silica solid sphere, nanovaccine, cancer immunotherapy