Contrast ultrasound targeted treatment of gliomas in mice via drug-bearing nanoparticle delivery and microvascular ablation.
Contrast ultrasound targeted treatment of gliomas in mice via drug-bearing nanoparticle delivery and microvascular ablation.
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DOI：
10.3791/2145
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发表时间：
2010-12-15
期刊：
影响因子：
--
通讯作者：
Price, Richard J
中科院分区：
文献类型：
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作者：
Burke, Caitlin W;Price, Richard J
我们正在开发基于微创造影剂微泡的治疗方法，其中微血管的渗透和/或消融由不同的超声脉冲参数控制。具体来说，我们正在测试这种方法是否可以通过药物输送和微血管消融来治疗恶性脑肿瘤。已经进行了初步研究，以确定超声介导的“复合”递送剂是否可以促进靶向药物承载纳米颗粒的递送，该递送剂由粘附在白蛋白壳微泡上的100纳米聚乳酸-羟基乙酸（PLAGA）纳米颗粒组成。我们将这些剂称为微泡-纳米颗粒复合剂（MNCAs）。当超声靶向皮下C6胶质瘤时，我们观察到在MNCA治疗的肿瘤中，纳米颗粒的递送量比用微泡和纳米颗粒共同治疗的肿瘤立即增加4.6倍，比未治疗的肿瘤增加8.5倍。此外，在许多癌症应用中，我们认为在肿瘤微循环消融的同时进行靶向药物递送可能是可取的，这将导致肿瘤缺氧和细胞凋亡。为此，我们测试了非热空化诱导的微血管消融的疗效，表明这种方法引起肿瘤灌注减少、细胞凋亡、显著的生长抑制和坏死。综上所述，这些结果表明我们的超声靶向方法有可能通过微血管消融和/或同时增强胶质瘤的药物负荷来提高治疗效率。
We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas.