A nanosystem for tumor treatment and imaging

用于肿瘤治疗和成像的纳米系统

• 批准号: 9037631
• 负责人: ERKKI RUOSLAHTI
• 金额: $ 40.46万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9037631
• 关键词: Apoptotic; Bacteriophages; Blood Circulation; Blood Vessels; Cardiovascular system; Cells; Collection; Contrast Media; Coupling; Data; Diffuse; Disease; Disseminated Malignant Neoplasm; Failure; Glioblastoma; Health; Homing; Image; Legal patent; Libraries; Magnetic Resonance Imaging; Measures; Mitochondria; Modality; Modeling; Mus; PECAM1 gene; Peptides; Perfusion; Pharmaceutical Preparations; Property; Refractory; Resistance; Surface; System; Ultrasonography; base; cancer therapy; cancer type; human disease; improved; iron oxide; malignant breast neoplasm; mouse model; nanoparticle; nanosystems; new technology; novel; particle; prevent; receptor; tumor; tumor growth

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.

描述（由申请人提供）：转移性癌症带来了巨大的治疗挑战。该应用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（GMB）的治疗方法，在肿瘤的弥漫性侵袭性方面与人类疾病非常相似。治疗方式是一种新颖的纳米系统，我们用它来对这些肿瘤进行令人印象深刻的控制。该纳米系统由促凋亡肽组成，通过将其与纳米颗粒表面偶联而变得非常有效，纳米颗粒通过肿瘤归巢肽引导至肿瘤。这种归巢肽还导致颗粒内化到靶细胞中。它还具有将有效负载递送至线粒体的独特特性，线粒体是促凋亡肽的目标。此外，氧化铁成分还可用作 MRI 造影剂。尽管 GBM 模型中的许多其他尝试治疗完全失败，但仍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标。 GBM 和乳腺癌的结果都提出了一个令人费解的悖论，即虽然我们能够破坏大部分传统的肿瘤脉管系统，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，接受治疗的肿瘤会发展出某种替代循环，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征，并开发针对其进行销毁的方法。这些研究将加深人们对肿瘤如何在破坏传统肿瘤脉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具有耐药性的癌症类型。