载药磁性复合微球用于HT-1080细胞的磁感应热化疗

Magnetic thermo-chemotherapy mediated by the doxorubicin-loaded magnetic composite microspheres on HT-1080 cells

目的:研究功能型载药磁性复合微球介导的磁感应热化疗对人纤维肉瘤细胞HT-1080的细胞毒性作用,为软组织肉瘤的治疗探索新方法。方法:双乳化法制备负载盐酸阿霉素(doxorubicin hydrochloride,DOX)和磁性颗粒(magnetic nanoparticles,MNPs)的磁性复合微球,仪器分析法对制备的复合微球进行理化性质表征测定,CCK8法检测细胞经不同处理后的相对增殖率,研究不同浓度的DOX及不同温度的水浴加热对HT-1080细胞的毒性作用,并以Veleriote法评价复合微球介导的磁感应热化疗是否存在协同增敏效应。结果:复合微球为粒径约3μm的光滑核壳结构的中空球体,MNPs及DOX分别位于微球的壳层和核层,该介质置于交变磁场下暴露可迅速升温,升温性能与微球中磁颗粒含量呈正相关性。单独DOX药物处理和加热处理对细胞均有毒性作用。DOX联合43℃热疗的细胞毒性效果优于单一药物或加热处理,复合微球介导的化疗和磁感应热化疗对肿瘤细胞的杀伤效果均优于单一DOX处理效果,热化疗之间存在协同增敏效应,该效应为非剂型依赖且复合微球介导的热化疗协同效应更为显著。结论:载药磁性复合微球可介导肿瘤磁感应热化疗,对HT-1080的细胞毒性呈热化疗协同效应。

Objective：To explore a novel protocol of comprehensive treatment for soft tissue sarcoma HT - 1080 cells, and to investigate the in vitro cytotoxicity of magnetic therrno - chemotherapy mediated by the doxorubicin - loaded magnetic composite microspheres. Methods： Double - emulsion method was applied for the preparation of doxorubicin - loaded magnetic nanocomposite microspheres. The physiochemical characterizations of the as - synthe- sized microspheres were systematically carried out by various instrumental analyses. Cells were subjected to various treatments, including drug treatment ,water bath hyperthermia and thermoehemotherapy treatment medicated by the mi- crospheres under AMF exposure. Cell relative growth rate（RGR） was evaluated by CCK8 assay, and the synergistic effects were analyzed by Veleriote method. Results： The doxorubicin - loaded magnetic composited microspheres were hollow core -shell structured spheres with an approximate size of around 3μm. MNPs and Doxorubicin were located within the shell and the core structures, respectively. Upon exposure under the AMF, the microspheres demonstrate ex- cellent inductive hearing property and there was a positive correlation between such property with the content of MNPs within the microspheres. The relative growth rate of the cells showed significant cytotoxicity of DOX treatment and wa- ter bath hyperthermia. The cytotoxicity of DOX combined with 43℃ water bath hyperthermia was more effective than mono - modal treatment. Compare of the free drug treatment by doxorubicin, chemotherapy and thermochemotherapy mediated by the drug loaded microspheres can induce an even lower relative growth rate of the HT - 1080 cells. There existed synergistic effect between doxorubicin and heating treatment and the effect was dose independent and more sig- nificant with the microsphere formulation. Conclusion： The doxorubicin -loaded magnetic composited microspheres can mediate magnetic thermochemotherapy, and the synergistic effect on HT - 1080 cells between heating treatment and drug treatment was confirmed.