磁感应纳米热化疗用于肿瘤综合治疗的体外研究

摘要

目的:研究磁性纳米粒子(magnetic nanoparticles,MNPs)介导的肿瘤纳米热疗联合甲氨蝶呤(Methotrexate,MTX)对乳腺癌细胞的体外毒性,为治疗乳腺癌探索新方法.方法:制备MNPs并对其进行表面修饰,对修饰前后的MNPs进行透射电子显微镜(TEM)、红外光谱分析(FTIR)、磁化曲线(VSM)、升温性能等一系列的理化表征.体外细胞实验选用人乳腺癌MCF-7细胞,采用CCK8试剂盒检测细胞活力.探讨磁场对细胞增殖能力的影响,以及不同浓度甲氨蝶呤对细胞的毒性作用,最后探讨甲氨蝶呤与水浴热疗、磁感应热疗联合应用对肿瘤细胞的杀伤作用,并评价是否具有热化疗协同效应.结果:一系列理化性质表征表明氨基硅烷修饰后的磁性纳米粒子呈近球形,粒径在10nm左右,具有超顺磁性和良好的升温性能.体外细胞实验结果表明,磁场暴露不会对MCF-7细胞活力造成影响.热疗对甲氨蝶呤具有一定的协同作用,热疗与甲氨蝶呤的联合应用可以更大力度的杀伤乳腺癌细胞.结论:MNPs联合甲氨蝶呤用于肿瘤综合治疗优于单一治疗.%Objective: To explore a novel protocol of comprehensive treatment for breast cancer, and investigate the in vitro cytotoxicity of magnetic thermochemotherapy mediated by magnetic nanoparticles combined with methotrexate ( MTX) ,an anti - cancer drug, for human breast cancer line MCF -7. Methods: Amino silane coated magnetic nanoparticles (MNPs) as agent of magnetic nanothermotherapy was prepared and the physiochemical characterizations on MNPs have been systematically carried out by various instrumental analyses, including TEM,FTIR as well as VSM. Inductive heating property of the MNPs was evaluated by monitoring the temperature increase of the MNPs suspension under an alternative magnetic field. Cells were subjected to various treatments, including AMF exposure, drug treatment , heating treatment ( both water - bath heating and magnetic heating) and themochemotherapy treatment by heating combined with MTX. Cell viability was evaluated by CCK8 assay. Results:The as -synthesized amino silane coated MNPs were nearly spherical in shape with an approximate size of around 10 nm. MNPs were superparamagnetic and with excellent inductive heating property under AMF exposure. The in - vitro cytotoxicity results on human breast cancer cell MCF - 7 by CCK8 assay indicated AMF exposure had negligible effect on cell viability. The bi - modal cancer treatment approach for combined magnetic nanothermotherapy and chemotherapy was more effective than mono - modal treatment, indicating a thermal enhancement effect of hyperthermia on drug cytocoxicity. Conclusion : The magnetic thermochemotherapy mediated by MNPs combined with methotrexate can realize cancer comprehensive treatment thus has great potential in clinical application.