磁共振引导聚焦超声破坏血脑屏障后脂质体阿霉素增强大鼠脑胶质瘤的抗肿瘤作用。
Improved anti-tumor effect of liposomal doxorubicin after targeted blood-brain barrier disruption by MRI-guided focused ultrasound in rat glioma.
机构信息
Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA.
出版信息
Ultrasound Med Biol. 2012 Oct;38(10):1716-25. doi: 10.1016/j.ultrasmedbio.2012.04.015. Epub 2012 Jul 19.
Abstract
The blood-brain barrier (BBB) inhibits the entry of the majority of chemotherapeutic agents into the brain. Previous studies have illustrated the feasibility of drug delivery across the BBB using focused ultrasound (FUS) and microbubbles. Here, we investigated the effect of FUS-enhanced delivery of doxorubicin on survival in rats with and 9L gliosarcoma cells inoculated in the brain. Each rat received either: (1) no treatment (control; N = 11), (2) FUS only (N = 9), (3) IV liposomal doxorubicin (DOX only; N = 17), or (4) FUS with concurrent IV injections of liposomal doxorubicin (FUS+DOX; N = 20). Post-treatment by magnetic resonance imaging (MRI) showed that FUS+DOX reduced tumor growth compared with DOX only. Further, we observed a modest but significant increase in median survival time after a single treatment FUS+DOX treatment (p = 0.0007), whereas neither DOX nor FUS had any significant impact on survival on its own. These results suggest that combined ultrasound-mediated BBB disruption may significantly increase the antineoplastic efficacy of liposomal doxorubicin in the brain.
摘要
血脑屏障（BBB）抑制了大多数化疗药物进入大脑。先前的研究已经说明了使用聚焦超声（FUS）和微泡跨越 BBB 进行药物递送的可行性。在这里，我们研究了 FUS 增强的阿霉素递送对脑内接种 9L 神经胶质瘤细胞的大鼠生存的影响。每只大鼠接受以下治疗之一：（1）无治疗（对照组；N=11），（2）仅 FUS（N=9），（3）IV 脂质体阿霉素（仅 DOX；N=17），或（4）FUS 联合 IV 注射脂质体阿霉素（FUS+DOX；N=20）。磁共振成像（MRI）显示，FUS+DOX 治疗后肿瘤生长减少。此外，我们观察到单次 FUS+DOX 治疗后中位生存时间略有但显著延长（p=0.0007），而 DOX 或 FUS 单独治疗均对生存没有显著影响。这些结果表明，联合超声介导的 BBB 破坏可能显著提高脑内脂质体阿霉素的抗肿瘤疗效。
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