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    NOVEL VEGF MIMETIC PEPTIDE-BASED SCAFFOLDS FOR THERAPEUTIC ANGIOGENESIS AND METHODS FOR THEIR USE
    1.
    发明申请
    NOVEL VEGF MIMETIC PEPTIDE-BASED SCAFFOLDS FOR THERAPEUTIC ANGIOGENESIS AND METHODS FOR THEIR USE 审中-公开
    用于治疗性血管生成的新型VEGF基于胶质细胞的药物及其使用方法

    公开(公告)号：WO2012149515A2

    公开(公告)日：2012-11-01

    申请号：PCT/US2012/035723

    申请日：2012-04-29

    Applicant: NORTHWESTERN UNIVERSITY ,  WEBBER, Matthew J. ,  TONGERS, Jorn ,  LOSORDO, Douglas W. ,  STUPP, Samuel I.

    Inventor： WEBBER, Matthew J. ,  TONGERS, Jorn ,  LOSORDO, Douglas W. ,  STUPP, Samuel I.

    IPC: A61K38/18

    CPC classification number: C07K14/001 ,  A61K38/18 ,  C07K14/52 ,  C07K2319/00

    Abstract: There is great demand for the development of novel therapies for ischemic cardiovascular disease, a leading cause of morbidity and mortality worldwide. Disclosed herein is a completely synthetic cell-free therapy based on peptide amphiphile nanostructures designed to mimic the activity of vascular endothelial growth factor (VEGF), one of the most potent angiogenic signaling proteins. Following self-assembly of peptide amphiphiles, nanoscale filaments form that display on their surfaces a VEGF mimetic peptide at high density. The VEGF-mimetic filaments disclosed herein were found to induce phosphorylation of VEGF receptors and induce pro-angiogenic behavior in endothelial cells, indicated by an enhancement in proliferation, survival and migration in vitro. In a chicken embryo assay, these nanostructures were found to promote an angiogenic response in the host vasculature. When evaluated in a mouse hind-limb ischemia model, the nanofibers were found to increase tissue perfusion, functional recovery, limb salvage, and treadmill endurance compared to controls, which include the VEGF mimetic peptide alone. Immunohistological evidence also demonstrated an increase in the density of microcirculation in the ischemic hind-limb, suggesting the mechanism of efficacy of this promising new therapy is linked to enhanced microcirculatory angiogenesis.

    Abstract translation: 对于缺血性心血管疾病的新型疗法的发展有很大的需求，这是全球发病率和死亡率的主要原因。 本文公开了一种完全合成的无细胞疗法，其基于设计用于模拟血管内皮生长因子（VEGF）活性的肽两亲性纳米结构，血管内皮生长因子（VEGF）是最有效的血管生成信号蛋白之一。 在肽两亲物的自组装之后，形成在其表面上以高密度显示VEGF模拟肽的纳米级丝。 发现本文公开的VEGF-模拟细丝诱导VEGF受体的磷酸化并诱导内皮细胞中的促血管生成行为，由体外增殖，存活和迁移的增强指示。 在鸡胚胎测定中，发现这些纳米结构在主体脉管系统中促进血管生成反应。 当在小鼠后肢缺血模型中进行评估时，与对照组相比，发现纳米纤维增加组织灌注，功能恢复，肢体打捞和跑步机耐力，其中包括单独的VEGF模拟肽。 免疫组织学证据也证实了缺血后肢微循环密度的增加，这表明这种有希望的新疗法的功效机制与增强的微循环血管生成有关。

    ENCAPSULATED PEPTIDE AMPHIPHILE NANOSTRUCTURES
    2.
    发明申请
    ENCAPSULATED PEPTIDE AMPHIPHILE NANOSTRUCTURES 审中-公开
    包封肽AMPHIPHILE NANOSTRUCTURES

    公开(公告)号：WO2008063808A2

    公开(公告)日：2008-05-29

    申请号：PCT/US2007/082417

    申请日：2007-10-24

    Applicant: NORTHWESTERN UNIVERSITY ,  LEE, Hyung-kun ,  SOUKASENE, Stephen ,  STUPP, Samuel, I.

    Inventor： LEE, Hyung-kun ,  SOUKASENE, Stephen ,  STUPP, Samuel, I.

    IPC: A61K38/10

    CPC classification number: A61K38/10 ,  A61K9/1278

    Abstract: The present invention provides compositions and methods for creating encapsulated peptide amphiphilic nanostructures useful in treating diseases. In particular, the present invention provides compositions and methods for preparing peptide amphiphile nanostructures that are encapsulated in liposomes by the application of light, and using such compositions in treating diseases, such as cancer.

    Abstract translation: 本发明提供用于产生用于治疗疾病的包封的肽两亲性纳米结构的组合物和方法。 特别地，本发明提供了通过应用光来制备封装在脂质体中的肽两亲物纳米结构的组合物和方法，并且使用这些组合物治疗诸如癌症的疾病。

    CHARGED PEPTIDE-AMPHIPHILE SOLUTIONS & SELF-ASSEMBLED PEPTIDE NANOFIBER NETWORKS FORMED THEREFROM
    7.
    发明申请
    CHARGED PEPTIDE-AMPHIPHILE SOLUTIONS & SELF-ASSEMBLED PEPTIDE NANOFIBER NETWORKS FORMED THEREFROM 审中-公开
    充电肽 - AMPHIPHILE解决方案和自组装肽纳米纤维网络

    公开(公告)号：WO2004018628A2

    公开(公告)日：2004-03-04

    申请号：PCT/US2003/026178

    申请日：2003-08-21

    Applicant: NORTHWESTERN UNIVERSITY ,  STUPP, Samuel, I. ,  SPOERKE, Erik, D. ,  ANTHONY, Shawn, G. ,  NIECE, Krista, L.

    Inventor： STUPP, Samuel, I. ,  SPOERKE, Erik, D. ,  ANTHONY, Shawn, G. ,  NIECE, Krista, L.

    IPC: C12N

    CPC classification number: B82Y30/00 ,  A61K38/00 ,  C07K7/08 ,  C07K14/78 ,  C07K2319/00 ,  Y10S977/795

    Abstract: The present invention provides a system of self-assembling peptide amphiphiles with an absolute net charge of 3 or greater whose design and function may be patterned after proteins involved in vertebrate mineralization or other tissue forming processes. This molecular system preferably consists of a hydrophobic hydrocarbon tail attached to a relatively hydrophilic peptide sequence. Self-assembly of this peptide amphiphile may be induced through pH variation, divalent ion addition, or dehydration. Variations of structural peptide sequences in the peptide amphiphile may enable the assembled nanofibers to be reversibly cross-linked for more or less structural stability, or may allow for control of the rate of self-assembly.

    Abstract translation: 本发明提供了一种具有3或更大的绝对净电荷的自组装肽两亲物的系统，其设计和功能可以在参与脊椎动物矿化或其它组织形成过程的蛋白质之后被图案化。 该分子系统优选由连接到相对亲水的肽序列的疏水性烃尾组成。 该肽两亲物的自组装可以通过pH变化，二价离子加成或脱水来诱导。 肽两亲物中的结构肽序列的变化可以使组装的纳米纤维可逆地交联以达到或多或少的结构稳定性，或者可以允许控制自组装速率。

    PEPTIDE AMPHIPHILE SOLUTIONS AND SELF ASSEMBLED PEPTIDE NANOFIBER NETWORKS
    8.
    发明申请
    PEPTIDE AMPHIPHILE SOLUTIONS AND SELF ASSEMBLED PEPTIDE NANOFIBER NETWORKS 审中-公开
    肽多肽溶液和自组装肽纳米纤维网络

    公开(公告)号：WO03084980A2

    公开(公告)日：2003-10-16

    申请号：PCT/US0310051

    申请日：2003-04-02

    Applicant: UNIV NORTHWESTERN ,  STUPP SAMUEL I ,  HARTGERINK JEFFREY D ,  BENIASH ELIA

    Inventor： STUPP SAMUEL I ,  HARTGERINK JEFFREY D ,  BENIASH ELIA

    IPC: A61K38/00 ,  C07K7/06 ,  C07K

    CPC classification number: C07K7/06 ,  A61K38/00

    Abstract: Peptide amphiphile self assembly and gelation to form nanofiber networks having cells within the network are described. The molecular structure of peptide amphiphiles and compositions including them suitable for forming nanofiber networks with cells under physiological conditions are also described. Methods to incorporate dissociated cells into self-assembled peptide amphiphile gels for molding of implants, in situ molding in animals, and injection of peptide amphiphile and cell compositions into an animal for tissue engineering and tissue repair applications are disclosed. The methods and compositions of the present invention are used to grow animal cells in a self assembled nanofiber network.

    Abstract translation: 描述了肽两亲物自组装和凝胶化以形成在网络内具有细胞的纳米纤维网络。 还描述了肽两亲物的分子结构以及包括它们适合于在生理条件下用细胞形成纳米纤维网络的组合物的组合物。 公开了将解离的细胞掺入自组装肽两亲物凝胶中以模塑植入物，在动物中原位模塑以及将肽两亲物和细胞组合物注射到动物中以进行组织工程和组织修复的应用。 本发明的方法和组合物用于在自组装纳米纤维网络中生长动物细胞。

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