NIR Absorbing Nanoparticles For Cancer Therapy

描述（由申请人提供）：50多年来，癌症一直是美国第二大死亡原因，占人口死亡人数的25%以上。每年诊断出的病例超过100万例，导致50多万例死亡（美国癌症协会，2001年）。纳米技术可能为癌症的诊断和治疗提供新的选择。我们的实验室正在研究一种新的基于纳米粒子的癌症治疗方法。由于血管渗漏和/或靶向，静脉注射近红外吸收纳米颗粒，并允许其在肿瘤中积聚，随后用近红外（NIR）光照射动物。近红外光不被组织成分明显吸收，允许深入穿透而不损害正常组织。使用一种被称为金-二氧化硅纳米壳的吸收nir的纳米颗粒，我们已经证明了肿瘤完全消融和肿瘤不再生的动物长期存活。我们最近开始了另外两类吸收近红外的纳米粒子的体外研究——金-金硫化纳米壳和金纳米棒。在体外，我们已经能够用这两种新型纳米颗粒实现更快的加热，因为它们具有更高的吸收和更低的散射（加热顺序，纳米棒，金-金硫化纳米壳，金-二氧化硅纳米壳），因此我们相信它们在低剂量的癌症治疗中比金-二氧化硅纳米壳更有效。然而，这三类纳米颗粒的大小差别很大。金-硅纳米壳的直径约为100纳米，金-金硫化物纳米壳的直径约为50纳米，金纳米棒的直径约为20纳米。因此，颗粒的生物分布将会非常不同，并可能极大地影响治疗效果。我们拟对这些nir吸收纳米粒子的生物分布、生物相容性和肿瘤消融效果进行评价。最佳颗粒配方将在成神经管细胞瘤模型中进一步检验。

DESCRIPTION (provided by applicant): For over fifty years, cancer has remained the second leading cause of death in the United States, accounting for over 25% of the deaths in the population. More than one million cases are diagnosed each year, resulting in over 500,000 deaths (American Cancer Society, 2001). Nanotechnology may offer new options for both diagnosis and treatment of cancer. A new nanoparticle-based approach to cancer therapy has been under investigation in our laboratory. Near infrared-absorbing nanoparticles are injected intravenously and allowed to accumulate in the tumor, due to the leaky vasculature and/or targeting, followed by illumination of the animal with near infrared (NIR) light. NIR light is not appreciably absorbed by tissue components, allowing deep penetration without damage to normal tissues. Using a class of NIR-absorbing nanoparticles called gold-silica nanoshells, we have demonstrated complete tumor ablation and long term survival of animals without tumor regrowth. We have recently begun in vitro studies with two other classes of NIR- absorbing nanoparticles - gold-gold sulfide nanoshells and gold nanorods. In vitro, we have been able to achieve much more rapid heating with these two newer types of nanoparticles due to their higher absorption and lower scattering (order of heating, nanorods, gold-gold sulfide nanoshells, gold-silica nanoshells), and thus believe that they have the potential to be more effective at lower doses in cancer therapy than gold- silica nanoshells. However, the sizes of these three classes of nanoparticles varies widely. Gold-silica nanoshells are approximately 100 nm in diameter, gold-gold sulfide nanoshells approximately 50 nm, and gold nanorods 20 nm. Thus, biodistribution of the particles will be quite different and may drastically affect therapeutic efficacy. We propose to evaluate biodistribution, biocompatibility and tumor ablation efficacy of these NIR-absorbing nanoparticles. The optimal particle formulation will be further examined in a model of medulloblastoma.