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本文报道以葡聚糖为中间载体,采用间接交联法制备胃癌单抗与抗癌药物(平阳霉素、柔红霉素、阿霉素及丝裂霉素C)的结合物。首先葡聚糖经氧化生成多醛基葡聚糖,利用其暴露的醛基与药物及单抗的氨基反应,形成希夫氏碱,最后用硼氢化钠还原,生成稳定的单抗—葡聚糖—药物三元结合物。经测算,结合物中每分子抗体可携带20—79个药物分子。体外研究表明:在结合物制备过程中,单抗活性无损失;且结合物稳定性好;结合物对肿瘤靶细胞具有较强的选择性细胞毒作用,优于游离药物及无关抗体结合物,对非靶细胞则毒性很弱。在荷瘤裸鼠体内放射免疫显像及生物学分布研究表明,结合物能选择性地定位于肿瘤组织,在局部达到较高浓度。
In this paper, we reported that dextran was used as an intermediate carrier to prepare a combination of gastric cancer monoclonal antibody and anticancer drugs (Pingyangmycin, daunorubicin, doxorubicin, and mitomycin C) by indirect cross-linking. First, dextran is oxidized to form polyaldehyde-based glucan. The exposed aldehyde group reacts with the amino group of the drug and the monoclonal antibody to form Schiff’s base, and finally it is reduced with sodium borohydride to form a stable monoclonal antibody. Sugar-drug ternary conjugates. It is estimated that each molecule of the conjugate can carry 20-79 drug molecules. In vitro studies showed that during the preparation of the conjugate, there was no loss of the activity of the monoclonal antibody; the conjugate had good stability; the conjugate had a strong selective cytotoxic effect on the tumor target cells, superior to the free drug and irrelevant antibody conjugate, The toxicity is weak for non-target cells. The radioimmunoscintigraphy and biodistribution studies in tumor-bearing nude mice showed that the conjugates can be selectively localized in tumor tissues and reach higher concentrations locally.