A nanosystem for tumor treatment and imaging

描述(申请人提供)：转移性癌症是一个巨大的治疗挑战。这一应用是基于我们努力开发新技术来处理侵袭性和转移性癌症的治疗。我们开发了一种治疗胶质母细胞瘤(GMBs)的方法，在肿瘤的弥漫侵袭性方面与人类疾病非常相似。这种治疗方式是一种新的纳米系统，我们已经使用它来获得对这些肿瘤的令人印象深刻的控制程度。该纳米系统由一种促凋亡多肽组成，通过将其偶联到纳米颗粒表面而使其高度有效，纳米颗粒由肿瘤归巢多肽引导至肿瘤。这种归巢多肽还会导致颗粒内化到靶细胞中。此外，它还具有将有效载荷传递给线粒体的独特特性，线粒体是促凋亡肽的靶标。此外，氧化铁成分还用作MRI造影剂。在GBM模型中的其他一些治疗尝试完全失败的情况下，取得了有希望的治疗结果。最近，我们已经证明乳腺癌也是纳米系统的一个很好的靶点。GBM和乳腺癌的结果都提出了一个令人费解的悖论：虽然我们能够摧毁大多数传统的肿瘤血管，但在侵袭性肿瘤模型中，小鼠最终会死于这种疾病。初步结果表明，接受治疗的肿瘤会形成某种替代循环，使它们对纳米系统的进一步治疗产生抵抗力。我们建议描述这种替代循环的特点，并开发以其为目标的销毁方法。这些研究将增加对肿瘤如何存活的理解，抗血管生成和血管破坏治疗破坏了传统的肿瘤血管系统。这些结果还可能产生更有效的癌症治疗方法，包括对目前所有可用的治疗方法基本上都具有抗药性的癌症类型。

DESCRIPTION (provided by applicant): Metastatic cancer poses a formidable treatment challenge. This application is based on our efforts to develop new technology to deal with treatment of invasive and metastatic cancer. We developed a treatment of glioblastomas (GMBs) that closely mimic the human disease with regard to the diffuse invasiveness of the tumors. The treatment modality is a novel nanosystem we have used to obtain an impressive degree of control over these tumors. The nanosystem consists of a pro-apoptotic peptide made highly potent by coupling it to the surface of nanoparticles, which are guided to the tumors by a tumor-homing peptide. This homing peptide also causes internalization of the particles into the target cells. It further has the unique property of delivering the payload to the mitochondria, which are the target of the pro-apoptotic peptide. Additionally, the iron oxide component served as an MRI contrast agent. The promising treatment results were achieved in the face of a complete failure of a number of other attempted treatments in the GBM models. More recently, we have shown that breast cancer is also a good target for the nanosystem. Both the GBM and breast cancer results have brought up the puzzling paradox that while we are able to destroy most of the conventional tumor vasculature, the mice ultimately succumb to the disease in the aggressive tumor models. Preliminary results suggest that the treated tumors develop some kind of alternative circulation that makes them resistant to further treatment with the nanosystem. We propose to characterize this alternative circulation and develop ways of targeting it for destruction. These studies will increase the understanding of how tumors survive anti-angiogenic and vascular disrupting treatments that destroy the conventional tumor vasculature. The results may also yield more efficacious treatments for cancers, including cancer types that are essentially resistant to all currently available treatments.