Kossatz Susanne, Ludwig Robert, Dähring Heidi, Ettelt Volker, Rimkus Gabriella, Marciello Marzia, Salas Gorka, Patel Vijay, Teran Francisco J, Hilger Ingrid
Institute for Diagnostic and Interventional Radiology I, Jena University Hospital - Friedrich Schiller University Jena, Bachstraße 18, 07740, Jena, Germany,
Pharm Res. 2014 Dec;31(12):3274-88. doi: 10.1007/s11095-014-1417-0. Epub 2014 Jun 3.
Tumor cells can be effectively inactivated by heating mediated by magnetic nanoparticles. However, optimized nanomaterials to supply thermal stress inside the tumor remain to be identified. The present study investigates the therapeutic effects of magnetic hyperthermia induced by superparamagnetic iron oxide nanoparticles on breast (MDA-MB-231) and pancreatic cancer (BxPC-3) xenografts in mice in vivo.
Superparamagnetic iron oxide nanoparticles, synthesized either via an aqueous (MF66; average core size 12 nm) or an organic route (OD15; average core size 15 nm) are analyzed in terms of their specific absorption rate (SAR), cell uptake and their effectivity in in vivo hyperthermia treatment.
Exceptionally high SAR values ranging from 658 ± 53 WgFe (-1) for OD15 up to 900 ± 22 WgFe (-1) for MF66 were determined in an alternating magnetic field (AMF, H = 15.4 kAm(-1) (19 mT), f = 435 kHz). Conversion of SAR values into system-independent intrinsic loss power (ILP, 6.4 ± 0.5 nHm(2)kg(-1) (OD15) and 8.7 ± 0.2 nHm(2)*kg(-1) (MF66)) confirmed the markedly high heating potential compared to recently published data. Magnetic hyperthermia after intratumoral nanoparticle injection results in dramatically reduced tumor volume in both cancer models, although the applied temperature dosages measured as CEM43T90 (cumulative equivalent minutes at 43°C) are only between 1 and 24 min. Histological analysis of magnetic hyperthermia treated tumor tissue exhibit alterations in cell viability (apoptosis and necrosis) and show a decreased cell proliferation.
Concluding, the studied magnetic nanoparticles lead to extensive cell death in human tumor xenografts and are considered suitable platforms for future hyperthermic studies.
肿瘤细胞可通过磁性纳米颗粒介导的加热被有效灭活。然而，用于在肿瘤内部提供热应激的优化纳米材料仍有待确定。本研究调查了超顺磁性氧化铁纳米颗粒诱导的磁热疗对小鼠体内乳腺（MDA-MB-231）和胰腺癌（BxPC-3）异种移植瘤的治疗效果。
对通过水相（MF66；平均核心尺寸12纳米）或有机路线（OD15；平均核心尺寸15纳米）合成的超顺磁性氧化铁纳米颗粒的比吸收率（SAR）、细胞摄取及其在体内热疗治疗中的有效性进行了分析。
在交变磁场（AMF，H = 15.4 kA·m⁻¹（19 mT），f = 435 kHz）中测定的SAR值极高，OD15的SAR值范围为658±53 W·gFe⁻¹，MF66高达900±22 W·gFe⁻¹。将SAR值转换为与系统无关的固有损耗功率（ILP，OD15为6.4±0.5 nH·m²·kg⁻¹，MF66为8.7±0.2 nH·m²·kg⁻¹），证实与最近发表的数据相比，其加热潜力明显更高。瘤内注射纳米颗粒后的磁热疗在两种癌症模型中均导致肿瘤体积显著减小，尽管以CEM43T90（43℃下的累积等效分钟数）测量的应用温度剂量仅在1至24分钟之间。对磁热疗治疗的肿瘤组织进行的组织学分析显示细胞活力（凋亡和坏死）发生改变，且细胞增殖减少。
总之，所研究的磁性纳米颗粒导致人肿瘤异种移植瘤中广泛的细胞死亡，被认为是未来热疗研究的合适平台。
