Novel Vehicles for Targeted Cardiovascular Repair

用于靶向心血管修复的新型载体

基本信息

批准号：
8858674
负责人：
Melina Rae Kibbe
金额：
$ 110.38万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-04 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8858674
关键词：
Adverse effects Arteries Atherosclerosis Balloon Angioplasty Biocompatible Biomedical Engineering Biomimetics Blood Blood Vessels Bypass Cardiology Cardiovascular Diseases Cardiovascular system Carotid Arteries Cause of Death Cell physiology Cells Cessation of life Coronary Coronary Arteriosclerosis Data Development Disease Drug Delivery Systems Endarterectomy Engineering Fibroblasts Goals Gold Health Hemorrhage High Density Lipoproteins Human Hyperplasia In Vitro Incidence Indium Individual Inflammation Injectable Injection of therapeutic agent Injury Intervention Interventional radiology Malignant Neoplasms Modality Modeling Molecular Mus Operative Surgical Procedures Patient risk Patients Peptides Peripheral arterial disease Pharmaceutical Preparations Pharmacotherapy Prevalence Preventive Procedures Property Public Health Rattus Research Research Personnel Rheumatology Risk Safety Secondary to Shapes Site Smooth Muscle Myocytes Specificity Stents Stream Structure Surface Technology Therapeutic Therapeutic Agents Time Translational Research Treatment Efficacy United States Vascular Endothelial Cell aging population biomaterial compatibility cell type chemical property combat design disability femoral artery in vivo innovation multidisciplinary nano nanoparticle nanoscale new technology novel particle prevent protein aminoacid sequence repaired restenosis stent thrombosis success targeted treatment therapeutic target therapy design therapy development

项目摘要

DESCRIPTION (provided by applicant): Atherosclerosis remains the leading cause of death and disability in the United States. Current therapeutic modalities for the treatment of severe coronary and peripheral artery disease include balloon angioplasty and stenting, endarterectomy, or bypass grafting. Unfortunately, a large number of these procedures fail due to the development of arterial restenosis secondary to neointimal hyperplasia. The overall goal of this Bioengineering Research Partnership (BRP) is to develop highly innovative targeted therapeutics delivered by bio-inspired tailorable constructs to prevent restenosis following vascular interventions. We expect to develop biocompatible nano- and microscale therapies that will be delivered systemically at the time of arterial intervention, target the manipulated arteria segment, and deliver molecular therapies and drugs to that site to inhibit restenosis. Each of the three platforms proposed are bio-inspired and share common physicochemical properties such that unique aspects of each one may be leveraged by the others to achieve maximal therapeutic efficacy. Preliminary data demonstrate the successful synthesis and in vivo targeting of a novel injectable peptide amphiphile (PA) to the site of vascular injury following intra-arterial injectio. We have also designed a biomimetic high density lipoprotein (HDL) using a gold nanoparticle (AuNP) as a template to control the size, shape, and surface chemical properties of the formed HDL AuNPs. Lastly, micron scale cell- like structures has been synthesized to mimic elements in the blood stream. Overall, we hypothesize that novel; targeted bioengineered therapeutic agents will prevent the development of restenosis following arterial interventions. To investigate this hypothesis, the specific aims are as follows: 1) synthesize and characterize novel bio-inspired delivery vehicles that are targeted to the site of vascular injury and deliver effective therapeutic agents; 2) evaluate the effect of the targeted engineered therapeutic delivery vehicles on cells from the vascular wall in vitro; 3) determine the specificity, safety, biocompatibility, and efficacy of the targeted engineered therapeutic delivery vehicles at inhibiting neointimal hyperplasia in vivo. Through our multidisciplinary team of investigators, we have already accrued preliminary data that supports the feasibility of our approach. With the support of this BRP, we will provide targeted therapies to prevent restenosis for patients undergoing any vascular intervention. These therapies could revolutionize how atherosclerotic arteries are treated and thus represent a paradigm-shifting technology. Finally, the bioengineered therapies developed in this proposal will be targeted to multiple cell types. Thus, project success will profoundly impact the fields of interventional cardiology, interventional radiology, cardiothoracic surgery, and vascular surgery, but will have more broad ranging impact in the fields of preventive cardiology, cancer, inflammation, and rheumatology.

描述（由申请人提供）：动脉粥样硬化仍然是美国死亡和残疾的主要原因。目前治疗严重冠状动脉和外周动脉疾病的治疗方式包括球囊血管成形术和支架置入术、动脉内膜切除术或旁路移植术。不幸的是，由于新内膜增生继发动脉再狭窄，许多这些手术都失败了。该生物工程研究合作伙伴关系 (BRP) 的总体目标是开发高度创新的靶向疗法，通过生物启发的可定制结构提供，以预防血管干预后的再狭窄。我们期望开发生物相容性的纳米和微米级疗法，这些疗法将在动脉介入时系统地递送，针对被操纵的动脉段，并将分子疗法和药物递送到该部位以抑制再狭窄。所提出的三个平台中的每一个都是受生物启发的，并且具有共同的物理化学特性，因此每个平台的独特方面可以被其他平台利用以实现最大的治疗功效。初步数据表明，一种新型可注射肽两亲物（PA）已成功合成并在体内靶向动脉内注射后的血管损伤部位。我们还设计了一种仿生高密度脂蛋白（HDL），使用金纳米颗粒（AuNP）作为模板来控制形成的HDL AuNP的尺寸、形状和表面化学性质。最后，微米级的细胞样结构已被合成以模拟血流中的元素。总的来说，我们假设那本小说；靶向生物工程治疗剂将预防动脉介入治疗后发生再狭窄。为了研究这一假设，具体目标如下：1）合成并表征新型仿生递送载体，靶向血管损伤部位并递送有效的治疗药物； 2) 评估靶向工程化治疗递送载体对体外血管壁细胞的作用； 3) 确定靶向工程治疗递送载体在抑制体内新生内膜增生方面的特异性、安全性、生物相容性和功效。通过我们的多学科研究团队，我们已经积累了支持我们方法可行性的初步数据。在该BRP的支持下，我们将为接受任何血管介入治疗的患者提供靶向治疗以预防再狭窄。这些疗法可能会彻底改变动脉粥样硬化的治疗方式，从而代表一种范式转变的技术。最后，该提案中开发的生物工程疗法将针对多种细胞类型。因此，项目的成功将深刻影响介入心脏病学、介入放射学、心胸外科和血管外科领域，并将在预防心脏病学、癌症、炎症和风湿病学领域产生更广泛的影响。