Mitoxantrone-Iron Oxide Biodistribution in Blood, Tumor, Spleen, and Liver-Magnetic Nanoparticles in Cancer Treatment
Mitoxantrone-Iron Oxide Biodistribution in Blood, Tumor, Spleen, and Liver-Magnetic Nanoparticles in Cancer Treatment
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DOI：
10.1016/j.jss.2011.01.060
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发表时间：
2012-06-01
影响因子：
2.2
通讯作者：
Wagner, Wolfgang
中科院分区：
文献类型：
--
作者：
Krukemeyer, Manfred G.;Krenn, Veit;Wagner, Wolfgang
背景。磁性药物靶向是一种新的肿瘤治疗原理，使用细胞抑制剂与铁磁纳米粒子和体外磁铁相结合。应实现肿瘤组织中较高的浓度、较低的全身浓度并且不损害健康器官。材料和方法。 n = 42 只成年 Wag/Rij 大鼠的右侧腓肠肌中转染了横纹肌肉瘤 R1H。在生物分布试验（n = 36）中，在使用或不使用体外 0.6 特斯拉磁铁和常规米托蒽醌的血浆和肿瘤组织中测量一剂和两剂给药时米托蒽醌-氧化铁的浓度。在血浆铁试验中 (n = 6)，在给药前、给药期间和给药后 30 分钟内测量血浆中的铁浓度。试验7天后，获取肝脏、脾脏和肿瘤样本并进行组织学评估。结果。当将磁铁放置在肿瘤区域上时，血浆中米托蒽醌氧化铁浓度显着降低（P < 0.05），并且与未偶联的米托蒽醌一样低。与未偶联的米托蒽醌相比，磁性药物靶向的肿瘤组织中的米托蒽醌浓度总是显着更高。两个剂量导致药物在肿瘤组织中蓄积。首次给药时血浆铁浓度升高。使用磁铁后，血浆水平降至起始水平以下。移除磁铁后，观察到随着铁浓度升高出现反弹现象。治疗后7天，肿瘤显示新鲜坏死，肝脏和脾脏有可检测到的铁沉积，但没有坏死。未观察到过敏或毒性反应。结论。我们发现，与血液相比，磁性药物靶向在肿瘤组织中实现了更高浓度的细胞抑制剂。在磁性药物靶向过程中，铁颗粒被快速清除并保留在肿瘤区域。网状内皮系统的器官不受细胞抑制损伤的影响。 (C) 2012 Elsevier Inc. 保留所有权利。
Background. Magnetic drug targeting is a new treatment principle for tumors using cytostatics coupled to ferrogmagnetic nanoparticles and extracorporeal magnets. Higher concentrations in tumor tissue with lower systemic concentrations and without damage of healthy organs should be achieved.Materials and Methods. n = 42 adult Wag/Rij rats were transfected with rhabdomyosarcoma R1H in their right gastrocnemius muscle. In the biodistribution trial (n = 36) concentrations of mitoxantrone-iron oxide with and without an extracorporeal 0.6 tesla magnet and regular mitoxantrone were measured in plasma and tumor tissue for one- and two-dose administration. In the plasma iron trial (n = 6) iron concentrations were measured in plasma before, during, and up to 30 min after drug administration. Seven days after the trial liver, spleen and tumor samples were obtained and histologically assessed.Results. Mitoxantrone iron-oxide concentration in plasma was significantly (P < 0.05) lower when a magnet was placed over the tumor area and as low as un-coupled mitoxantrone. Mitoxantrone concentration in tumor tissue was always significantly higher with magnetic drug targeting when compared with un-coupled mitoxantrone. Two doses resulted in drug accumulation in tumor tissue. Plasma iron concentrations rose when the drug was first administered. Plasma levels fell below the starting level with a magnet applied. A rebound phenomenon with rising iron concentrations was observed after the magnet was removed. Tumors showed fresh necrosis and liver and spleen had detectable iron depositions but no necrosis 7 d after treatment. No allergies or toxic reactions were observed.Conclusions. We showed that magnetic drug targeting achieves higher concentrations of cytostatics in tumor tissue compared with blood. During magnetic drug targeting, iron particles are quickly sluiced and kept in the tumor area. Organs of the reticuloendothelial system are not affected by cytostatic damage. (C) 2012 Elsevier Inc. All rights reserved.