Magnetic nanoparticle hyperthermia enhances radiation therapy: A study in mouse models of human prostate cancer.

Magnetic nanoparticle hyperthermia enhances radiation therapy: A study in mouse models of human prostate cancer.
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DOI:
10.3109/02656736.2015.1005178
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发表时间:
2015-06
期刊:
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
影响因子:
--
通讯作者:
Ivkov R
Ivkov R
中科院分区:
其他
文献类型:
--
作者:
Attaluri A;Kandala SK;Wabler M;Zhou H;Cornejo C;Armour M;Hedayati M;Zhang Y;DeWeese TL;Herman C;Ivkov R

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我们的目的是表征前列腺癌放射治疗 (RT) 的磁性纳米粒子热疗 (mNPH)。人类前列腺癌皮下肿瘤 PC3 和 LAPC-4 在雄性裸鼠中生长。当肿瘤测量时,将 150 mm3 磁性氧化铁纳米颗粒 (MIONP) 注射到肿瘤中,目标剂量为 5.5 mg Fe/cm3 肿瘤,并在 24 小时后通过暴露于交变磁场 (AMF) 进行治疗。将小鼠随机分配到四个队列之一,以表征(1)肿瘤内 MIONP 分布,(2)可变热剂量 mNPH(固定 AMF 峰值振幅 24 kA/m,160±5 kHz)有/无 RT(5 Gy)的影响,(3)RT 的影响(RT5:5 Gy;RT8:8 Gy),以及(4)固定热剂量 mNPH(43 °C,20 分钟)有/无 RT (5 Gy)。分别使用电感耦合等离子体质谱 (ICP-MS) 和普鲁士蓝染色在处死和收获组织后评估 MIONP 浓度和分布。监测并比较治疗组之间的肿瘤生长。 LAPC-4 肿瘤比 PC3 肿瘤保留了更高的 MIONP 浓度和更均匀的分布。 AMF功率调制为mNPH组和联合治疗组提供了相似的热剂量(CEM43:LAPC-4:33.6±3.4与25.9±0.8,PC3:27.19±0.7与27.50±0.6),从而克服了MIONP分布的局限性,并产生统计学上显着的肿瘤生长延迟。 PC3 和 LAPC-4 肿瘤代表两种生物模型,展示了不同的纳米颗粒保留和分布模式,提供了一个模型来比较 mNPH 的这些影响。 mNPH 的调制功率提供了克服 MIONP 分布限制以增强 mNPH 的潜力。
We aimed to characterise magnetic nanoparticle hyperthermia (mNPH) with radiation therapy (RT) for prostate cancer. Human prostate cancer subcutaneous tumours, PC3 and LAPC-4, were grown in nude male mice. When tumours measured 150 mm3 magnetic iron oxide nanoparticles (MIONPs) were injected into tumours to a target dose of 5.5 mg Fe/cm3 tumour, and treated 24 h later by exposure to alternating magnetic field (AMF). Mice were randomly assigned to one of four cohorts to characterise (1) intratumour MIONP distribution, (2) effects of variable thermal dose mNPH (fixed AMF peak amplitude 24 kA/m at 160±5 kHz) with/without RT (5 Gy), (3) effects of RT (RT5: 5 Gy; RT8: 8 Gy), and (4) fixed thermal dose mNPH (43 °C for 20min) with/without RT (5 Gy). MIONP concentration and distribution were assessed following sacrifice and tissue harvest using inductively coupled plasma mass spectrometry (ICP-MS) and Prussian blue staining, respectively. Tumour growth was monitored and compared among treated groups. LAPC-4 tumours retained higher MIONP concentration and more uniform distribution than did PC3 tumours. AMF power modulation provided similar thermal dose for mNPH and combination therapy groups (CEM43: LAPC-4: 33.6 ± 3.4 versus 25.9 ± 0.8, and PC3: 27.19 ± 0.7 versus 27.50 ± 0.6), thereby overcoming limitations of MIONP distribution and yielding statistically significant tumour growth delay. PC3 and LAPC-4 tumours represent two biological models that demonstrate different patterns of nanoparticle retention and distribution, offering a model to make comparisons of these effects for mNPH. Modulating power for mNPH offers potential to overcome limitations of MIONP distribution to enhance mNPH.