Eynali Samira, Khoei Samideh, Khoee Sepideh, Esmaelbeygi Elaheh
a Department of Medical Physics and Biomedical Engineering, School of Medicine , Tehran University of Medical Sciences , Tehran , Iran.
b Department of Medical Physics, School of Medicine , Iran University of Medical Sciences , Tehran , Iran.
Int J Hyperthermia. 2017 May;33(3):327-335. doi: 10.1080/02656736.2016.1243260. Epub 2016 Oct 23.
The purpose of this study was to evaluate the combined effects of heat and polylactic-co-glycolic acid (PLGA) nanoparticles, as 5-fluorouracil carriers with/without iron oxide core, on the viability and proliferation capacity of human colon cancer cell line HT-29 in the spheroid model. HT-29 spheroid cells were treated with different concentrations of 5-FU or 5-FU-loaded into both nanoparticles for 74 h. Hyperthermia was then performed at 43 °C for 60 min. Finally, the effects of the mentioned treatments on cell viability and proliferation capacity were evaluated using the trypan blue dye exclusion test and colony formation assay, respectively. Our results showed that hyperthermia, in combination with 5-FU or PLGA nanoparticles as 5-FU carriers, significantly enhanced the cytotoxic effects as compared to the control group. Considering that nanoparticles could increase the intracellular concentration of drugs in cancer cells, the extent of cytotoxic effects following treatment with 5-FU-loaded into both nanoparticles was significantly higher than that with free 5-FU. In addition, the presence of iron oxide cores in nanoparticles during hyperthermia enhanced the cytotoxic effects of hyperthermia compared with nanoparticles without iron oxide core. Based on this study, hyperthermia in combination with 5-FU-loaded PLGA nanoparticles with iron oxide core drastically reduced the proliferation capacity of HT-29 cells; therefore, it may be considered as a new direction in the treatment of colon cancer.
本研究的目的是评估热疗与聚乳酸-乙醇酸共聚物(PLGA)纳米颗粒(有无氧化铁核心作为5-氟尿嘧啶载体)联合作用对人结肠癌细胞系HT-29在球体模型中的活力和增殖能力的影响。将HT-29球体细胞用不同浓度的5-氟尿嘧啶(5-FU)或负载于纳米颗粒中的5-FU处理74小时。然后在43°C下进行60分钟的热疗。最后,分别使用台盼蓝染料排除试验和集落形成试验评估上述处理对细胞活力和增殖能力的影响。我们的结果表明,与对照组相比,热疗与作为5-FU载体的5-FU或PLGA纳米颗粒联合使用可显著增强细胞毒性作用。考虑到纳米颗粒可增加癌细胞内药物浓度,负载于纳米颗粒中的5-FU处理后的细胞毒性作用程度显著高于游离5-FU。此外,热疗期间纳米颗粒中存在氧化铁核心与无氧化铁核心的纳米颗粒相比,增强了热疗的细胞毒性作用。基于本研究,热疗与负载5-FU的含氧化铁核心的PLGA纳米颗粒联合使用可显著降低HT-29细胞的增殖能力;因此,它可能被视为结肠癌治疗的一个新方向。