International Journal of Nanomedicine (Apr 2020)
Antigen-Conjugated Silica Solid Sphere as Nanovaccine for Cancer Immunotherapy
Abstract
Ying Dong,1 Jing Gao,1 Mengyue Pei,2 Xiaoli Wang,2 Chuangnian Zhang,2 Yingjie Du,1 Yanjun Jiang1 1School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300130, People’s Republic of China; 2Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, People’s Republic of ChinaCorrespondence: Jing Gao; Xiaoli Wang Tel +86-22-60204945; +86-22-87890151Email [email protected]; [email protected]: 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
