目的 制备担载抗肿瘤药物阿霉素(doxorubicin,DOX)和磁性纳米颗粒(magnetic nanoparticles,MNP)的复合磁性碘化油微乳。通过体外实验评价其生物相容性及作为肝肿瘤栓塞热化疗介质的可行性。方法 对MNP进行改性处理,采用超声乳化的方法,将DOX、改性后的MNP及碘化油制成复合微乳。将该微乳置于交变磁场下暴露并检测其升温性能。体外实验采用小鼠成纤维细胞L-929和人肝肿瘤细胞HepG-2,并以CCK-8试剂盒检测细胞活力。探讨磁场对细胞增殖能力的影响,不同浓度DOX对细胞的毒性作用,以及担载DOX的纳米磁性碘化油微乳与磁感应热疗联合应用对肿瘤细胞的杀伤作用,并评价其是否具有热化疗协同增敏效应。结果 该介质在500kHz、60Gs的交变磁场下升温性能良好,满足热疗对温度的需求。生物相容性良好,符合医疗器械生物学评价国家标准的要求。磁感应热疗联合DOX化疗可更大力度地抑制肝肿瘤细胞的增殖,二者存在协同增敏效应。结论 本研究提出的载药纳米磁性碘化油微乳生物相容性良好,在交变磁场下可实现热化疗协同增敏效应,是一种肝肿瘤综合治疗的新型功能型介质。
Objective Drug-loaded magnetic nanocomposite iodized oil microemulsion was prepared by using the double emulsion method. The microemulsion contained anti-tumor drug doxorubicin(DOX),magnetic nanoparticles(MNP),and iodized oil as the matrix. The evaluation on biocompatibility and the feasibility of the nanocomposite microemulsion as the media for liver cancer comprehensive treatment was carried out in vitro. Methods MNPs modified with oleic acid,DOX and iodized oil were made of composite microemulsion by phacoemulsification. Inductive heating properties were evaluated by monitoring the temperature increase of the nanocomposite microemulsion under an alternative magnetic field (AMF). Mouse fibroblast cell L-929 and human liver hepatocellular carcinoma cell HepG-2 were employed in the study. HepG-2 cells were subjected to various treatments including AMF exposure,drug treatment,heating treatment as well as thermochemotherapy treatment medicated by the nanocomposite microemulsion. Cell viability was evaluated by CCK-8 assay. Results The nanocomposite microemulsion possessed excellent inductive heating property under AMF exposure which satisfied the temperature requirement during cancer hyperthermia. Cytotoxicity study showed that the biocompatibility of the microemulsion was good,which met the requirement to Evalution on biology of medical apparatus GB/T 16886. Conclusions The biocompatibility of the microemulsion containing DOX and MNPs is good. The bi-modal treatment with magnetic thermochemotherapy is more effective than mono-modal treatment. The synergistic effect between heating treatment and drug treatment was confirmed under AMF exposure. The nanocomposite microemulsion is a new functional media for comprehensive treatment of liver tumors.