Feasibility Study of Particle-Assisted Laser Ablation of Brain Tumors in Orthotopic Canine Model
Feasibility Study of Particle-Assisted Laser Ablation of Brain Tumors in Orthotopic Canine Model
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DOI：
10.1158/0008-5472.can-08-2535
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发表时间：
2009-02-15
期刊：
影响因子：
11.2
通讯作者：
Payne, J. Donald
中科院分区：
文献类型：
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作者：
Schwartz, Jon A.;Shetty, Anil M.;Payne, J. Donald
我们报告了一项初步研究，该研究显示了将纳米壳被动递送至原位肿瘤的概念证明，在原位肿瘤中，纳米壳诱导了与正常大脑不同的局部、受限的治疗反应，从而在犬脑模型中对犬传染性性病肿瘤（cTVT）进行光热消融。在严重联合免疫缺陷小鼠中生长的cTVT片段成功地接种在免疫抑制的混合品种猎犬的顶叶中。静脉输注单剂量的近红外（NIR）吸收的150 mm纳米壳，并允许时间在颅内肿瘤中被动积累，这是原位脑转移的代表。纳米壳在颅内cTVT内积聚，表明其新生血管系统代表正常血脑屏障的中断。通过经皮、光纤递送的NIR辐射热消融肿瘤，使用808 nm的3.5 W平均3分钟激光剂量，选择性地将肿瘤组织的温度升高至65.8 +/- 4.1 ℃。相同的激光剂量应用于大脑对侧的正常白色和灰质，产生了48.6 +/- 1.1摄氏度的亚致死温度。激光剂量被设计为在不存在纳米壳的情况下最小化对正常脑组织的热损伤，并补偿肿瘤中纳米壳积累的可变性。处理的脑切片的死后组织病理学显示了纳米壳辅助热消融的有效性和选择性。[癌症研究2009：69（4）：1659-67]
We report on a pilot study showing a proof of concept for the passive delivery of nanoshells to an orthotopic tumor where they induce a local, confined therapeutic response distinct from that of normal brain resulting in the photothermal ablation of canine transmissible venereal tumor (cTVT) in a canine brain model. cTVT fragments grown in severe combined immunodeficient mice were successfully inoculated in the parietal lobe of immunosuppressed, mixed-breed hound dogs. A single dose of near-IR (NIR)-absorbing, 150-mm nanoshells was infused i.v. and allowed time to passively accumulate in the intracranial tumors, which served as a proxy for an orthotopic brain metastasis. The nanoshells accumulated within the intracranial cTVT, suggesting that its neovasculature represented an interruption of the normal blood-brain harrier. Tumors were thermally ablated by percutaneous, optical fiber-delivered, NIR radiation using a 3.5-W average, 3-minute laser dose at 808 nm that selectively elevated the temperature of tumor tissue to 65.8 +/- 4.1 degrees C. Identical laser doses applied to normal white and gray matter on the contralateral side of the brain yielded sublethal temperatures of 48.6 +/- 1.1 degrees C. The laser dose was designed to minimize thermal damage to normal brain tissue in the absence of nanoshells and compensate for variability in the accumulation of nanoshells in tumor. Postmortem histopathology of treated brain sections showed the effectiveness and selectivity of the nanoshell-assisted thermal ablation. [Cancer Res 2009:69(4):1659-67]