Jordan A, Wust P, Scholz R, Tesche B, Fähling H, Mitrovics T, Vogl T, Cervós-Navarro J, Felix R
Department of Radiation Oncology, Virchow University Clinic, Humboldt Universität zu Berlin, Germany.
Int J Hyperthermia. 1996 Nov-Dec;12(6):705-22. doi: 10.3109/02656739609027678.
Suspensions of coated superparamagnetic particles (magnetic fluids, MF) in AC magnetic fields have a pronounced specific absorption rate (SAR) per mass compared to multidomain particles. The aim of the present study was to investigate cellular uptake and the biological effects of AC magnetic field excited bio-compatible magnetic fluids on human carcinoma cells in vitro. One of the fluids tested was a dextran magnetite, which has a very low cyto-toxicity with survival fractions (SF) between 0.8 and 0.9 at concentrations of up to 5 mg ferrite per ml. Human carcinoma cells intracellularly accumulate up to 1 pg ferrite/cell which has been demonstrated by electron microscopy (TEM), X-ray spectroscopy and measurements of intracellular iron. It has been shown that the ferrite core is not altered intracellularly, but many of the dextran shells are degraded which yields particle chains and other aggregates observed in TEM. Semi-solid pellets of the tumour cells were treated with AC magnetic fields (520 kHz, 4-12.5 kA/m) or waterbath hyperthermia at 43 and 45 degrees C, in presence of extracellular and/or intracellular magnetic fluid particles. Although MF heating is produced from individual particles, the survival fractions of MF heated and water bath heated cells are equal. In fact, the extracellular MF particle distribution is homogeneous enough to obtain similar inactivation. In contrast to earlier reports intracellular dextran magnetite particles in AC magnetic fields did not induce cell inactivation. Since the amount of intracellular ferrite should be indeed large enough for cell inactivation, the loss of dextran shells is most probably the main cause of limited effectiveness of the intracellular magnetite particles. The present work has demonstrated that: (1) MFH is able to inactivate tumour cells in vitro to at least the same extent as water bath hyperthermia; and (2) that there is a sensitizer effect of ferrofluids at 43 degrees C probably caused by free ferric ions which induce oxidative stress; and (3) that there is no cytotoxic effect of intracellular dextran magnetite particles 30-180 min excited with AC magnetic fields used in this study. For the new method the term 'magnetic fluid hyperthermia (MFH)' is proposed.
与多畴颗粒相比，包覆超顺磁性颗粒（磁流体，MF）在交流磁场中的悬浮液具有显著的单位质量比吸收率（SAR）。本研究的目的是研究交流磁场激发的生物相容性磁流体对人癌细胞的细胞摄取和生物学效应。所测试的一种流体是葡聚糖磁铁矿，其细胞毒性非常低，在每毫升高达5毫克铁氧体的浓度下，存活分数（SF）在0.8至0.9之间。人癌细胞在细胞内积累高达1皮克铁氧体/细胞，这已通过电子显微镜（TEM）、X射线光谱和细胞内铁的测量得到证实。已经表明，铁氧体核心在细胞内没有改变，但许多葡聚糖壳被降解，这产生了TEM中观察到的颗粒链和其他聚集体。在细胞外和/或细胞内存在磁流体颗粒的情况下，用交流磁场（520 kHz，4 - 12.5 kA/m）或43和45摄氏度的水浴热疗处理肿瘤细胞的半固体沉淀物。尽管MF加热是由单个颗粒产生的，但MF加热和水浴加热细胞的存活分数是相等的。事实上，细胞外MF颗粒分布足够均匀，以获得相似的失活效果。与早期报告相反，交流磁场中的细胞内葡聚糖磁铁矿颗粒并未诱导细胞失活。由于细胞内铁氧体的量确实应该足够大以导致细胞失活，葡聚糖壳的损失很可能是细胞内磁铁矿颗粒有效性有限的主要原因。目前的工作表明：（1）MFH能够在体外使肿瘤细胞失活，其程度至少与水浴热疗相同；（2）在43摄氏度时，铁磁流体存在敏化作用，可能是由诱导氧化应激的游离铁离子引起的；（3）本研究中使用的交流磁场激发30 - 180分钟的细胞内葡聚糖磁铁矿颗粒没有细胞毒性作用。对于这种新方法，提出了“磁流体热疗（MFH）”这一术语。
