抗原偶联二氧化硅实心球作为癌症免疫治疗的纳米疫苗。
Antigen-Conjugated Silica Solid Sphere as Nanovaccine for Cancer Immunotherapy.
机构信息
School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300130, People's Republic of China.
Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, People's Republic of China.
出版信息
Int J Nanomedicine. 2020 Apr 22;15:2685-2697. doi: 10.2147/IJN.S242463. eCollection 2020.
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.
背景
纳米载体可以向抗原呈递细胞 (APC) 输送大量抗原，这在癌症免疫治疗中具有很大的刺激体液和细胞反应的潜力。此后，制备了硅酸钠固体纳米球 (SiO)，并将模型抗原 (卵清蛋白，OVA) 共价偶联到 SiO 表面形成纳米疫苗 (OVA@SiO)。并评估了 OVA@SiO 用于癌症免疫治疗的应用。
材料与方法
采用 Stöber 法制备 SiO 固体纳米球，然后依次用氨丙基三乙氧基硅烷胺化，用戊二醛活化。将 OVA 共价偶联到活化的 SiO 表面，得到纳米疫苗（OVA@SiO）。通过动态光散射、扫描电子显微镜和透射电子显微镜来鉴定 OVA@SiO 的粒径分布、zeta 电位和形态。通过改变戊二醛浓度来研究 OVA 的载药量。通过 Cell Counting Kit-8 测定法评估 OVA@SiO 对 DC2.4 和 RAW246.7 细胞的生物相容性。评估了 OVA@SiO 被 DC2.4 摄取及其内化途径在不存在或存在不同抑制剂的情况下的情况。还研究了 OVA@SiO 对骨髓来源的 DC 细胞的激活和成熟作用。最后，评价了 OVA@SiO 的体内转运及其对器官的毒性。
结果
所有结果均表明 OVA 成功地共价偶联到 SiO 表面。所制备的 OVA@SiO 具有高抗原载量，对 APCs 和主要器官具有良好的生物相容性。此外，OVA@SiO 促进了 DC2.4 细胞摄取抗原及其胞质释放。值得注意的是，OVA@SiO 显著促进了树突状细胞的成熟和共给药佐剂 CpG-ODN 上调细胞因子分泌。
结论
所制备的 SiO 显示出作为抗原递送载体的有前途的潜力。
Zotero 插件