磁靶向定位灌注化疗膀胱癌磁性吡柔比星纳米粒的制备与评价

摘要

目的：构建一种新型的磁靶向定位灌注化疗膀胱癌的吡柔比星纳米制剂，并探讨其磁靶向定位及抗膀胱癌细胞特性，为定位灌注化疗膀胱癌的临床应用提供帮助。方法通过N－N′－羰基二咪唑（CDI）交联剂将治疗膀胱癌的临床药物吡柔比星（ pirarubicin，THP）连接在表面氨基化的四氧化三铁（ Fe3 O4）磁性纳米粒上，制备具有磁性的THP纳米制剂，并在体外考察其磁定位性能和对膀胱癌细胞的抑制作用。结果THP成功地连接到了粒径40 nm左右的Fe3 O4磁性纳米粒上，磁性药物制剂在不同pH值的缓冲液中药物在90％以上，并可在外界磁场作用下定位于靶向部位。对膀胱癌细胞可造成THP和Fe3 O4双重抑制效果，抑制率高达58．44％。结论该纳米制剂可通过外界磁场定位于靶向部位，膀胱癌细胞抑制效果明显，为临床定位灌注化疗的应用奠定了基础。%Objective We synthesized novel magnetic pirarubicin nanoparticles for targeted intravesical chemotherapy to treat bladder cancer .Methods Pirarubicin was grafted on Fe 3 O4 nanoparticles which were surface-functionalized with amino-groups via N, N′-Carbonyldiimidazoleas targeted intravesical infusion chemotherapy agents.Mimetic position in vitro by external magnetic field and inhibition to bladder cancer cells of prepared agents were demonstrated.Results Pirarubicin was successfully grafted on magnetic Fe3 O4 nanoparticles whose size were around 40 nm.The residual of pirarubicin on the pharmaceutic agents was above 90% in buffer solutions of various pH.They also could be positioned to certain area by external magnetic. Meanwhile, the prepared magnetic pirarubicin nanoparticles gave multiple-inhibition to bladder cancer cells by THP and Fe3 O4.The inhibition rate was up to 58.44% after co-cultured for 2 h.Conclusions These magnetic pirarubicin nanoparticles have a great potential for clinical use in infusion chemotherapy.