New synthetic aminooxy lipid was designed and synthesized as a building block for the formulation of functionalised nanoliposomes (presenting onto the outer surface of aminooxy groups) by microfluidic mixing. Orthogonal binding of cellular mannan (Candida glabrata (CCY 26-20-1) onto the outer surface of functionalised nanoliposomes was modified by orthogonal binding of reducing termini of mannans to oxime lipids via a click chemistry reaction based on aminooxy coupling (oxime ligation). The aminooxy lipid was proved as a suitable active component for preparation of functionalised nanoliposomes by the microfluidic mixing method performed with the instrument NanoAssemblr™. This “on-chip technology” can be easily scaled-up. The structure of mannan-liposomes was visualized by transmission and scanning electron microscopy, including immunogold staining of recombinant mannan receptor bound onto mannosylated-liposomes. The observed structures are in a good correlation with data obtained by DLS, NTA, and TPRS methods. In vitro experiments on human and mouse dendritic cells demonstrate selective internalization of fluorochrome-labelled mannan-liposomes and their ability to stimulate DC comparable to lipopolysaccharide. We describe a potentially new drug delivery platform for mannan receptor-targeted antimicrobial drugs as well as for immunotherapeutics. Furthermore, the platform based on mannans bound orthogonally onto the surface of nanoliposomes represents a self-adjuvanted carrier for construction of liposome-based recombinant vaccines for both systemic and mucosal routes of administration.

设计并合成了新的合成氨氧基脂质，作为通过微流体混合配制功能化纳米脂质体（呈现在氨氧基基团外表面上）的基础。通过基于氨基氧基偶联的肟化学反应（肟连接），通过还原甘露聚糖的末端与肟脂质的正交结合，修饰了细胞甘露聚糖（Candida glabrata（CCY 26-20-1））与功能化纳米脂质体外表面的正交结合。通过使用NanoAssemblr™仪器进行的微流体混合方法，证明了氨基氧基脂质是制备功能化纳米脂质体的合适活性成分，这种“芯片技术”可以很容易地按比例放大。透射和扫描电子显微镜 包括结合到甘露糖基化脂质体上的重组甘露聚糖受体的免疫金染色。观察到的结构与通过DLS，NTA和TPRS方法获得的数据具有良好的相关性。在人和小鼠树突状细胞上进行的体外实验表明，荧光染料标记的甘露聚糖脂质体的选择性内在化及其刺激DC的能力可与脂多糖媲美。我们描述了一种针对甘露聚糖受体靶向的抗菌药物以及免疫疗法的潜在新药递送平台。此外，基于正交结合到纳米脂质体表面上的甘露聚糖的平台代表了用于构建全身和粘膜给药途径的基于脂质体的重组疫苗的自佐剂载体。观察到的结构与通过DLS，NTA和TPRS方法获得的数据具有良好的相关性。在人和小鼠树突状细胞上进行的体外实验表明，荧光染料标记的甘露聚糖脂质体的选择性内在化及其刺激DC的能力可与脂多糖媲美。我们描述了一种针对甘露聚糖受体靶向的抗菌药物以及免疫疗法的潜在新药递送平台。此外，基于正交结合到纳米脂质体表面上的甘露聚糖的平台代表了用于构建全身和粘膜给药途径的基于脂质体的重组疫苗的自佐剂载体。观察到的结构与通过DLS，NTA和TPRS方法获得的数据具有良好的相关性。在人和小鼠树突状细胞上进行的体外实验表明，荧光染料标记的甘露聚糖脂质体的选择性内在化及其刺激DC的能力可与脂多糖媲美。我们描述了一种针对甘露聚糖受体靶向的抗菌药物以及免疫疗法的潜在新药递送平台。此外，基于正交结合到纳米脂质体表面上的甘露聚糖的平台代表了用于构建全身和粘膜给药途径的基于脂质体的重组疫苗的自佐剂载体。在人和小鼠树突状细胞上进行的体外实验表明，荧光染料标记的甘露聚糖脂质体的选择性内在化及其刺激DC的能力可与脂多糖媲美。我们描述了一种针对甘露聚糖受体靶向的抗菌药物以及免疫疗法的潜在新药递送平台。此外，基于正交结合到纳米脂质体表面上的甘露聚糖的平台代表了用于构建全身和粘膜给药途径的基于脂质体的重组疫苗的自佐剂载体。在人和小鼠树突状细胞上进行的体外实验表明，荧光染料标记的甘露聚糖脂质体的选择性内在化及其刺激DC的能力可与脂多糖媲美。我们描述了一种针对甘露聚糖受体靶向的抗菌药物以及免疫疗法的潜在新药递送平台。此外，基于正交结合到纳米脂质体表面上的甘露聚糖的平台代表了用于构建全身和粘膜给药途径的基于脂质体的重组疫苗的自佐剂载体。