Multiple treatments with liposomal doxorubicin and ultrasound-induced disruption of blood-tumor and blood-brain barriers improve outcomes in a rat glioma model.
Multiple treatments with liposomal doxorubicin and ultrasound-induced disruption of blood-tumor and blood-brain barriers improve outcomes in a rat glioma model.
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DOI：
10.1016/j.jconrel.2013.04.007
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发表时间：
2013-07-10
期刊：
影响因子：
--
通讯作者：
McDannold N
中科院分区：
文献类型：
--
作者：
Aryal M;Vykhodtseva N;Zhang YZ;Park J;McDannold N
血脑屏障（BBB）阻止大多数抗癌药物转运到中枢神经系统，并限制递送到浸润性脑肿瘤。肿瘤血管中的异质性血管渗透性，沿着其他几个因素，为脑肿瘤的药物治疗创造了额外的障碍。聚焦超声（FUS），当与循环微泡结合时，是一种新兴的非侵入性方法，暂时渗透血脑屏障和“血液肿瘤屏障”。在这里，我们测试了每周三次的FUS和脂质体阿霉素（DOX）在9 L大鼠胶质瘤肿瘤中的影响。接受FUS + DOX的动物（N = 8）的中位存活时间与仅接受DOX（N = 6）、仅接受FUS（N = 8）或不接受治疗（N = 7）的动物相比显著增加（P < 0.001）。接受FUS + DOX的动物的中位存活率相对于未治疗的对照组增加了100%，而仅接受DOX的动物仅改善了16%。仅接受FUS的动物没有表现出改善。在FUS + DOX组的4/8只动物中在组织学中未发现肿瘤细胞，并且在两只动物中，仅检测到少量肿瘤细胞。治疗组的不良事件包括皮肤毒性、活动受损、周围脑组织损伤和肿瘤部位的组织损失。在1只动物中观察到瘤内出血。这些事件在很大程度上与多柔比星的已知副作用和广泛的肿瘤负荷一致。总之，这项工作表明，使用这种FUS技术来增强脂质体阿霉素的递送的多个阶段在这种大鼠胶质瘤模型中具有显著的治疗效果。
The blood-brain-barrier (BBB) prevents the transport of most anticancer agents to the central nervous system and restricts delivery to infiltrating brain tumors. The heterogeneous vascular permeability in tumor vessels, along with several other factors, creates additional barriers for drug treatment for brain tumors. Focused ultrasound (FUS), when combined with circulating microbubbles, is an emerging noninvasive method to temporarily permeabilize the BBB and the “blood-tumor barrier”. Here, we tested the impact of three weekly sessions of FUS and liposomal doxorubicin (DOX) in 9L rat glioma tumors. Animals that received FUS + DOX (N = 8) had a median survival time that was increased significantly (P < 0.001) compared to animals who received DOX only (N = 6), FUS only (N = 8), or no treatment (N = 7). Median survival for animals that received FUS + DOX was increased by 100% relative to untreated controls, whereas animals who received DOX alone had only a 16% improvement. Animals who received only FUS showed no improvement. No tumor cells were found in histology in 4/8 animals in the FUS + DOX group, and in two animals, only a few tumor cells were detected. Adverse events in the treatment group included skin toxicity, impaired activity, damage to surrounding brain tissue, and tissue loss at the tumor site. In one animal, intratumoral hemorrhage was observed. These events are largely consistent with known side effects of doxorubicin and with an extensive tumor burden. Overall this work demonstrates that multiple sessions using this FUS technique to enhance the delivery of liposomal doxorubicin has a pronounced therapeutic effect in this rat glioma model.
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影响因子：
19.7
作者：
Hynynen, K;McDannold, N;Jolesz, FA
通讯作者：
Jolesz, FA
影响因子：
11.2
作者：
McDannold N;Arvanitis CD;Vykhodtseva N;Livingstone MS
通讯作者：
Livingstone MS
影响因子：
10.8
作者：
Geers, Bart;Lentacker, Ine;De Smedt, Stefaan C.
通讯作者：
De Smedt, Stefaan C.
影响因子：
3.5
作者：
McDannold, N;Vykhodtseva, N;Hynynen, K
通讯作者：
Hynynen, K
DOI：
10.1111/j.1754-9485.2010.02232.x
发表时间：
2011-02-01
影响因子：
1.6
作者：
Dobelbower, Michael C.;Burnett, Omer L., III;Fiveash, John B.
通讯作者：
Fiveash, John B.