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）：转移性癌症提出了巨大的治疗挑战。该应用是基于我们开发新技术来处理侵入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，该治疗与肿瘤的弥漫性侵入性密切模仿人类疾病。治疗方式是一种新型的纳米系统，我们用来获得对这些肿瘤的令人印象深刻的控制程度。纳米系统由促凋亡肽组成，通过将其耦合到纳米颗粒的表面，该肽由纳米颗粒的表面耦合，而纳米颗粒的表面通过肿瘤含有肿瘤的肽引导到肿瘤。这种归位肽还导致颗粒内部化到靶细胞中。它进一步具有将有效载荷传递给线粒体的独特属性，线粒体是促凋亡肽的靶标。另外，氧化铁成分充当MRI对比剂。面对GBM模型中许多其他尝试治疗的完全失败，实现了有希望的治疗结果。最近，我们表明乳腺癌也是纳米系统的良好目标。 GBM和乳腺癌的结果都引起了令人困惑的悖论，尽管我们能够破坏大多数常规肿瘤脉管系统，但在侵略性肿瘤模型中，小鼠最终屈服于该疾病。初步结果表明，经过治疗的肿瘤会产生某种替代性循环，使它们具有抵抗纳米系统的进一步治疗。我们建议表征这种替代性循环，并开发针对破坏的方法。这些研究将增加对肿瘤如何生存的抗血管生成和血管破坏治疗的理解，从而破坏常规肿瘤血管。结果还可能为癌症提供更有效的治疗方法，包括对所有当前可用治疗的癌症类型。