氟尿脱氧核苷键合聚阳离子载体的合成及其抗肿瘤活性研究

Preparation of floxuridine loaded polycation and its antitumor activity

目的:合成5-氟尿嘧啶的聚乙烯亚胺-β-环糊精的高分子前体药物,并研究其抗肿瘤活性。方法:将氟尿脱氧核苷(5-氟尿嘧啶的一种前体药物)偶合于聚乙烯亚胺-β-环糊精载体材料,得到5-氟尿嘧啶的高分子前体药物;用核磁共振氢谱(1H-NMR)、紫外光谱(UV)以及红外光谱(FT-IR)对其结构进行表征,并在人肝癌细胞HepG2上进行细胞毒性实验和细胞迁移实验。结果:1H-NMR、UV以及FT-IR的结果表明氟尿脱氧核苷已以共价键的方式偶合于聚乙烯亚胺-β-环糊精载体材料上;紫外光谱测得其载药率约为2%;细胞实验结果表明,该高分子前体药物对肿瘤有一定的药效,并且一定程度上抑制肿瘤细胞的迁移。结论:成功合成了聚乙烯亚胺-β-环糊精-氟尿脱氧核苷,其对人肝癌细胞HepG2表现出一定的抗肿瘤活性。

Objective： To develop a new prodrug of 5-fluorouracil-polyethylenimine-β-cyclodextrin-floxuridine （ PEI-β-CyD-Fd ） and to test its antitumor activity. Methods： Floxuridine was conjugated to polyethylenimine-β-cyclodextrin to form prodrug PEI-β-CyD Fd. The structure of synthesized PEI-β-CyD-Fd was confirmed by1H-NMR,FT-IR and UV. MTT assay and cell wound healing assay were performed on human hepatic carcinoma cell line HepG2. Results： The drug loading was 2%. The MTT assay and cell wound healing assay indicated that PEI-β-CyD-Fd significantly inhibited proliferation and migration of HepG2 cells. Conclusion： The synthesized prodrug PEI-CyD-Fd has a significant antitumor activity on HepG2 cells.