Data_Sheet_1_Proof of Concept Study: Mesoporous Silica Nanoparticles, From Synthesis to Active Specific Immunotherapy.PDF

Nanomaterials are increasingly valued tools in drug delivery research as they offer enhanced stability, controlled release and more effective drug encapsulation. Though yet to be introduced in clinical trial, mesoporous silica nanoparticles are promising delivery systems, due to their high chemical and mechanical stability while remaining biodegradable. This work provides proof of concept for particle based vaccines as cost-effective alternatives for dendritic cell immunotherapy. Synthesis and surface chemistry of the nanoparticles are optimized for protein conjugation and nanoparticles are characterized for their physicochemical properties and biodegradation. Ovalbumin is used as a model protein to load nanoparticles to produce a nanovaccine. The vaccine is tested in vitro on dendritic cultures to verify particle and vaccine uptake, toxicity, maturation effects and explicitly ovalbumin cross-presentation on MHC class I molecules. The optimized synthesis protocol renders reproducible mesoporous silica nanoparticles, resistant against agglomeration, within the required size range and have carboxylic surface functionalization necessary for protein conjugation. They are biodegradable over a time span of 1 week. This period is adjustable by changing synthesis parameters. UV sterilization of the particles does not induce quality loss, nor does it have toxic effects on cells. Treatment with mesoporous silica nanoparticles increases expression of MHC and costimulatory molecules of dendritic cells, indicating an adjuvant effect of nanoparticles on the adaptive immune system. Nanovaccine uptake and cross-presentation of ovalbumin are observed and the latter is increased when delivered by nanoparticles as compared to control conditions. This confirms the large potential of mesoporous silica nanoparticle based vaccines to replace dendritic-based active specific immunotherapy, offering a more standardized production process and higher efficacy.

纳米材料作为药物递送研究中的日益重要的工具，因其卓越的稳定性、可控的释放特性以及更有效的药物包封能力而备受推崇。尽管尚未应用于临床试验，但介孔二氧化硅纳米粒子作为一种具有高度化学和力学稳定性且可生物降解的潜在递送系统，展现出巨大的应用前景。本研究为基于粒子的疫苗作为树突状细胞免疫疗法的经济高效替代方案提供了概念验证。纳米粒子的合成和表面化学经过优化，以实现蛋白质偶联，并对纳米粒子的物理化学性质和生物降解性进行了表征。卵白蛋白被用作模型蛋白，用于负载纳米粒子以制备纳米疫苗。该疫苗在体外对树突状细胞培养进行测试，以验证粒子和疫苗的摄取、毒性、成熟效应以及卵白蛋白在MHC I类分子上的明确交叉呈递。优化的合成方案使得可重复制备的介孔二氧化硅纳米粒子具有抗聚集性，且在所需尺寸范围内，并具有蛋白质偶联所需的羧基表面官能团。这些纳米粒子在1周内可生物降解。该降解周期可通过改变合成参数进行调整。纳米粒子的紫外线灭菌不会引起质量损失，也不会对细胞产生毒性作用。介孔二氧化硅纳米粒子的治疗可增加树突状细胞的MHC和共刺激分子的表达，表明纳米粒子对适应性免疫系统的佐剂效应。观察到纳米疫苗的摄取和卵白蛋白的交叉呈递，并且与对照条件相比，通过纳米粒子递送时后者有所增加。这证实了基于介孔二氧化硅纳米粒子的疫苗具有巨大的潜力，可替代基于树突状细胞的主动特异性免疫疗法，提供更标准化的生产流程和更高的疗效。