Homhuan Atthachai, Kogure Kentaro, Akaza Hideyuki, Futaki Shiroh, Naka Takashi, Fujita Yukiko, Yano Ikuya, Harashima Hideyoshi
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo, Hokkaido, Japan.
J Control Release. 2007 Jul 16;120(1-2):60-9. doi: 10.1016/j.jconrel.2007.03.017. Epub 2007 Apr 1.
Despite the potential of mycobacterial cell wall (CW) components to serve as immunotherapeutic agents, this application is hampered by the molecules' unfavorable physicochemical properties, such as its high molecular weight, poor solubility and negatively charged nature. Here we describe a new mycobacterial CW delivery system that uses an efficient and simple packaging method. This is achieved by incorporating mycobacterial CW into liposomes and attaching arginine octamers (R8) to the liposome surface. R8-modified liposomes improve the uptake of mycobacterial CW by dendritic cells (DC) and enhance its immunostimulatory activity. High R8 surface density promoted high levels of mycobacterial CW uptake by DC compared to low density R8-modified liposomes. Maturation markers (CD80, CD86, MHC Class II molecules) showed significantly enhanced expression on DC pulsed with high density R8-modified liposomes containing mycobacterial CW. Moreover, R8-modified liposomes with mycobacterial CW incorporated induced production of IL-12 p40 by DC, at levels similar to those produced by lipopolysaccharide-pulsed DC. We assert that R8-modified liposomes with mycobacterial CW incorporated should have tremendous potential as immune-potentiating agents.
尽管分枝杆菌细胞壁（CW）成分具有作为免疫治疗剂的潜力，但该应用受到这些分子不利的物理化学性质的阻碍，例如其高分子量、低溶解度和带负电荷的性质。在这里，我们描述了一种新的分枝杆菌CW递送系统，该系统使用一种高效且简单的包装方法。这是通过将分枝杆菌CW掺入脂质体并将精氨酸八聚体（R8）连接到脂质体表面来实现的。R8修饰的脂质体提高了树突状细胞（DC）对分枝杆菌CW的摄取，并增强了其免疫刺激活性。与低密度R8修饰的脂质体相比，高R8表面密度促进了DC对分枝杆菌CW的高水平摄取。成熟标志物（CD80、CD86、II类主要组织相容性复合体分子）在被含有分枝杆菌CW的高密度R8修饰的脂质体脉冲处理的DC上显示出显著增强的表达。此外，掺入分枝杆菌CW的R8修饰的脂质体诱导DC产生IL-12 p40，其水平与脂多糖脉冲处理的DC产生的水平相似。我们断言，掺入分枝杆菌CW的R8修饰的脂质体作为免疫增强剂应该具有巨大的潜力。
