Department of Radio-Oncology, Radiation Hospital, Paracelsus Hospitals, Osnabrück, Germany.
J Surg Res. 2012 Jun 1;175(1):35-43. doi: 10.1016/j.jss.2011.01.060. Epub 2011 Mar 2.
Magnetic drug targeting is a new treatment principle for tumors using cytostatics coupled to ferromagnetic nanoparticles and extracorporeal magnets. Higher concentrations in tumor tissue with lower systemic concentrations and without damage of healthy organs should be achieved.
n = 42 adult Wag/Rij rats were transfected with rhabdomyosarcoma R(1)H 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.
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 uncoupled mitoxantrone. Mitoxantrone concentration in tumor tissue was always significantly higher with magnetic drug targeting when compared with uncoupled 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.
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 sliced and kept in the tumor area. Organs of the reticuloendothelial system are not affected by cytostatic damage.
磁性药物靶向治疗是一种利用与顺磁纳米颗粒偶联的细胞抑制剂治疗肿瘤的新方法，使用外加磁场可以将药物浓集于肿瘤组织而降低全身的药物浓度，同时减少对正常组织的损害。
42 只成年 Wag/Rij 大鼠右腓肠肌接种横纹肌肉瘤 R(1)H。在生物分布实验（n = 36）中，我们在单次和双剂量给予载药氧化铁和顺磁纳米颗粒及外加 0.6 特斯拉磁场和普通米托蒽醌后，测量血浆和肿瘤组织中的米托蒽醌-氧化铁浓度。在血浆铁浓度实验（n = 6）中，我们在给予药物前后及 30 分钟内测量血浆铁浓度。实验后 7 天，处死动物，取肝脏、脾脏和肿瘤组织进行组织学检查。
外加磁场时，载药氧化铁在血浆中的浓度显著降低（P < 0.05），与未偶联的米托蒽醌相近。当进行磁性药物靶向治疗时，肿瘤组织中米托蒽醌的浓度始终显著高于未偶联的米托蒽醌。双剂量治疗可使药物在肿瘤组织中聚集。给予药物后，血浆铁浓度升高。当外加磁场时，血浆铁浓度降至起始水平以下。去除磁场后，出现铁浓度回升的反弹现象。肿瘤组织出现新鲜坏死，肝脏和脾脏可见铁沉积，但无坏死。治疗后 7 天未见过敏或毒性反应。
我们的研究表明，与血液相比，磁性药物靶向治疗可以使肿瘤组织中的细胞抑制剂浓度更高。在进行磁性药物靶向治疗时，铁颗粒迅速被切割并保持在肿瘤区域，网状内皮系统的器官不受细胞抑制剂损害。
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