Practical development of the lipid vesicle as surfactant assemblies having a functional molecular-recognition -toward to a cancer therapy in DDS-

本工作的主要目的是制备一种新的脂质囊泡，该囊泡具有特异性靶向癌细胞的功能，可应用于DDS中的癌症治疗：该囊泡主要由Span80（山梨糖单油酸酯）组成，稳定性非常好。首先，选择新的海藻凝集素作为癌细胞的靶向配体作为“导弹装置”，将其固定在囊泡上。从一种红藻Eucheuma serra中提取并纯化了海藻凝集素。凝集素缩写为ESA （Eucheuma serra凝集素）。ESA特别与高甘露糖型碳水化合物链相关。esa动员的囊泡（简称ESA-vesicle）被发现能够特异性地与癌细胞结合，如人结肠腺癌（col201），而不能像正常细胞系那样与MCF10-2A和成纤维细胞结合。ESA具有良好的热稳定性和对癌细胞生长的抑制作用。因此，ESA既可用于靶向配体，也可用于肿瘤细胞或肿瘤细胞生长抑制剂。生长抑制还可诱导细胞凋亡。esa囊泡在兔上动脉内顺利飞行。esa -囊泡注射大鼠体内实验表明，由于大鼠在5周内没有体重减轻，囊泡对大鼠没有细胞毒性作用。此外，在携带col201的裸鼠体内注射esa囊泡的实验中，也观察到对col201的生长抑制作用。因此，esa囊泡有望用于DDS的肿瘤治疗。接下来，将上述几种抗体作为“导弹装置”也固定在Span80囊泡上。体外标记实验成功地证实了免疫囊泡与每个靶向细胞的特异性结合。将免疫囊泡中的DNA或质粒转染到靶细胞也得到了证实。因此，上述esa囊泡以及免疫囊泡有望应用于DDS或基因转染。少

The main purpose of this work is the new preparation of the lipid vesicles, which have a function of specific targeting to a cancer cell to apply to a cancer therapy in DDS : the vesicles are mainly composed of Span80 (sorbitan monooleate) and the stability is very excellent.First, as a targeting ligand to a cancer cell as "missile device" which was immobilized to the vesicle, new alga lectin was chosen. The alga lectin was extracted and purified from a red alga, Eucheuma serra. The lectin was abbreviated as ESA (Eucheuma serra agglutinin). The ESA associates with high-mannose type carbohydrate chain specifically. The ESA-imoobilized vesicle (abbreviated as ESA-vesicle) was found to specifically combine with cancer cells, such as human colon adenocarcinoma (colo201) and not to combine to MCF10-2A and Fibroblast as a normal cell lines. The ESA had an excellent heat-stability and the inhibition of the growth of a cancer cell. Thus, ESA can be applied to both the targeting ligand and canc … More er cell or the inhibitor of cancer-cell growth. The growth inhibition was also found to induce an apoptosis. The ESA-vesicle flew smoothly in the superior artery of rabbit.The in-vivo experiments on the injection of the ESA-vesicle into rats suggested no cytotoxic effect of the vesicle on the rats because of the rat's living during 5 weeks without decrease in the weight. Moreover, in the in-vivo experiments on the injection of the ESA-vesicle into the nude mouse carrying colo201, the growth inhibition of the colo201 was aiso observed. Thus, the ESA-vesicle is expected to using for the cancer therapy in DDS.Next, some kinds of antibodies as a "missile device" as mentioned above were also immobilized on the Span80 vesicle. The specifical combines of the immunovesicles with each targeting cell were successfully confirmed the tageting experiments in vitro. The transfection of the DNA or prasmid entrapped in the immunovesicles to the targeting cells were also confirmed.Thus, the above ESA-vesicles as well as an immunovesicle were expected to be applied to either DDS or gene transfection. Less