A nanosystem for tumor treatment and imaging

描述（由申请人提供）：转移性癌症是一项艰巨的治疗挑战。这一应用是基于我们开发新技术来治疗侵袭性和转移性癌症的努力。我们开发了一种胶质母细胞瘤（GMBs）的治疗方法，它在肿瘤的弥漫性侵袭方面与人类疾病非常相似。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。该纳米系统由促凋亡肽组成，通过将其偶联到纳米颗粒表面，使其具有很强的效力，纳米颗粒由肿瘤归巢肽引导到肿瘤中。这种归巢肽也会导致颗粒内化到靶细胞中。它还具有将有效载荷传递到线粒体的独特特性，线粒体是促凋亡肽的目标。此外，氧化铁成分作为MRI造影剂。这些有希望的治疗结果是在GBM模型中许多其他尝试治疗完全失败的情况下取得的。最近，我们已经证明乳腺癌也是纳米系统的一个很好的目标。GBM和乳腺癌的研究结果都提出了一个令人困惑的悖论：虽然我们能够破坏大多数传统肿瘤的血管系统，但在侵袭性肿瘤模型中，小鼠最终死于这种疾病。初步结果表明，接受治疗的肿瘤形成了某种替代循环，使它们对纳米系统的进一步治疗产生了抵抗力。我们建议描述这种替代循环的特征，并开发针对其进行破坏的方法。这些研究将增加对肿瘤如何在破坏常规肿瘤血管系统的抗血管生成和血管破坏治疗中存活的理解。研究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治疗方法基本上都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.