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目的用β-硫代酯键构建新型肿瘤靶向性喜树碱大分子前药以达到减毒增效的目的。方法首先用可控聚合和大分子改性的方法,得到新型肿瘤靶向性喜树碱大分子前药。用凝胶渗透色谱仪测试其分子量大小和分布;用光散射仪表征由其制备的靶向纳米粒子的粒径、分布和表面电势。用细胞毒性实验评估其对结直肠癌细胞HCT116的杀伤效果;用流式细胞仪测试细胞凋亡与细胞摄取的相关机制。结果在所得大分子前药中,喜树碱含量为11.0 wt%,粒径为87.6(±1.09)nm,表面电势为-6.8(±0.48)m V。在不含酯酶时,药物可稳定地连接在高分子上,可有效避免药物早释的问题;在酯酶存在时,可快速实现药物释放。其能有效地促进细胞对药物摄取并促进细胞凋亡。结论新型肿瘤靶向性喜树碱大分子前药可有效地提升喜树碱的抗肿瘤效果。
Objective To construct a new tumor-targeted camptothecin macromolecular prodrug with β-thioester to achieve the goal of attenuated and synergistic effect. Methods Firstly, a new type of tumor targeting camptothecin macromolecular prodrug was obtained by controlled polymerization and macromolecular modification. The size and distribution of molecular weight were measured by gel permeation chromatography. The particle size, distribution and surface potential of the prepared nanoparticles were characterized by light scattering. Cytotoxicity assay was used to evaluate the cytotoxicity against colorectal cancer cells HCT116. Flow cytometry was used to test the mechanism of apoptosis and cellular uptake. Results In the resulting macromolecular prodrugs, the content of camptothecin was 11.0 wt%, the particle size was 87.6 (± 1.09) nm and the surface potential was -6.8 (± 0.48) mV. In the absence of esterase, the drug can be stably linked to the polymer, which can effectively avoid the problem of early release of the drug; in the presence of esterase, the drug can be quickly released. It can effectively promote cell uptake of drugs and promote apoptosis. Conclusion The novel tumor targeting camptothecin macromolecular prodrug can effectively improve the anti-tumor effect of camptothecin.