基于酵母膜囊泡药物载体系统的构建与应用初探

Construction and preliminary application of drug carrier system based on yeast membrane vesicles

酿酒酵母作为可食用真核微生物,具有安全性高、增殖快、成本低、易改造等特性,已广泛用于生产疫苗、抗体、胰岛素等。截至目前,酵母相关组分如细胞壁、酵母微囊体已被广泛用于肿瘤、炎症病毒感染、创伤后骨关节炎等疾病的治疗。其中,酵母细胞膜组成成分相对简单稳定,易于大规模提取。因此,本研究以酵母细胞膜材料为研究对象,构建酵母膜囊泡纳米系统,并初步探究其生物医学应用。通过共挤出法制备酵母质膜囊泡(Saccharomyces cerevisiae membrane vesicle, SMV),并对SMV的粒径与表面电位、药物装载与释放特性、稳定性、细胞安全性、体外治疗效果等进行探究。结果显示:SMV平均粒径为185.1 nm,通过共孵育及超声等方法有效包载姜黄素及二氧化硅纳米粒,并保持细胞膜蛋白特性。而且SMV具有良好的稳定性与生物相容性。此外, SMV可被巨噬细胞RAW 264.7有效摄取,包载姜黄素的SMV可有效清除巨噬细胞内的活性氧(ROS)。综上,本研究所制备的酵母质膜囊泡可有效递送姜黄素药物及包载纳米粒,有效被巨噬细胞摄取并降低ROS,为酵母膜材料的生物医学应用提供了新思路和新方法。

As an edible eukaryotic microorganism,Saccharomyces cerevisiae has the characteristics of high safety,rapid proliferation,low cost,easy transformation,etc.It has been widely used to produce vaccines,antibodies,insulin,etc.Up to now,yeast components,such as cell wall and yeast microcapsules,have been widely used in the treatment of tumors,inflammatory virus infection,post-traumatic osteoarthritis and other diseases.Among them,the components of yeast cell membrane are relatively simple and stable,which are easy to be extracted on a large scale.Therefore,yeast cell membrane material was used to construct yeast membrane vesicle nanosystem,and its biomedical application was preliminarily explored.In this study,Saccharomyces cerevisiae membrane vesicle(SMV)was prepared by co-extrusion method,and the particle size and surface potential of SMV,drug loading and release characteristics,stability,cell safety,and in vitro therapeutic effect were investigated.The results showed that the average particle size of SMV was 185.1 nm.Curcumin and silica nanoparticles were effectively encapsulated by co-incubation and ultrasonic methods,and the characteristics of cell membrane proteins were maintained.Moreover,SMV had good stability and biocompatibility.In addition,SMV could be effectively uptaken by macrophages RAW 264.7,and curcumin loaded SMV could effectively eliminate reactive oxygen species(ROS).In conclusion,the yeast plasma membrane vesicles prepared in this study could effectively deliver curcumin drugs and encapsulate nanoparticles,and could be effectively absorbed by macrophages and effectively eliminate ROS,providing new ideas and new methods for biomedical applications of yeast membrane materials.