Novel nanoparticles to stimulate therapeutic angiogenesis in peripheral arterial disease

刺激外周动脉疾病治疗性血管生成的新型纳米颗粒

• 批准号: 10756875
• 负责人: RALPH P. MASON
• 金额: $ 5.97万
• 依托单位: UNIVERSITY OF TEXAS ARLINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-02 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10756875
• 关键词: Address; Adhesions; Adhesiveness; Adhesives; Affect; Affinity; American; Angioplasty; Aniline; Area; Arterial Injury; Arteries; Award; Balloon Angioplasty; Binding; Biological Availability; Blood Vessels; Blood flow; CD34 gene; Cell Proliferation; Characteristics; Circulation; Complementary DNA; Cytoprotection; Data; Development; Disease Management; Dopamine; Drug Delivery Systems; Drug Monitoring; Endothelial Cells; Endothelium; Ensure; Erythropoietin Receptor; Evaluation; Family suidae; Formulation; Fostering; Goals; Hyaluronic Acid; Hydrogels; In Vitro; Inflammatory Response; Investigation; Ischemia; Leg; Ligands; Membrane; Mentors; Modality; Modeling; Mussels; Nanotechnology; Obstruction; P-Selectin; Parents; Patients; Peripheral arterial disease; Pharmaceutical Preparations; Plasmids; Polymers; Procedures; Recovery; Research; Research Personnel; Site; Standardization; Stress; System; Techniques; Testing; Therapeutic; Therapeutic Agents; Time; Tissues; Treatment Effectiveness; Underrepresented Minority; Vascular Diseases; Vascularization; Work; aging population; angiogenesis; antibody conjugate; biomaterial compatibility; career development; controlled release; design; disadvantaged background; doctoral student; endothelial stem cell; equity, diversity, and inclusion; fluorescence imaging; fucoidan; healing; image guided; imaging capabilities; imaging modality; improved; injured; innovation; local drug delivery; minority student; nanocomposite; nanoparticle; nanoparticle delivery; novel; overexpression; parent grant; photoacoustic imaging; physically handicapped; recruit; systemic toxicity; therapeutic angiogenesis; therapeutic effectiveness; underrepresented minority student

Abstract The long-term goal of our parent grant award is to develop novel biocompatible and biodegradable dual-modal imaging nanoparticles (DINPs) to provide cell protection and to facilitate therapeutic angiogenesis under stress conditions such as ischemia for peripheral arterial disease (PAD). For this supplement application, we propose the following approaches aimed to enrich the potential of our parent award: a) the development of fucoidan (FC) targeted nanoparticles (FC-DINPs) with optimized fluorescent and photoacoustic imaging capabilities, b) the formulation of FC-DINP loaded hydrogel angioplasty balloon coatings for simultaneous percutaneous transluminal angioplasty and local drug delivery, and c) the evaluation of FC-DINPs transfer efficacy to ex-vivo segments of porcine arteries. The main innovative aspects of our design are: 1) the simultaneous angioplasty treatment and local delivery of therapeutic agents via a mussel-inspired nanocomposite balloon coating formed by the combination of FC-DINPs and adhesive hydrogels, to ensure a homogeneous and controlled drug delivery, 2) the use of biodegradable photoluminescent polymer-aniline tetramers (BPLPAT) to fabricate FC- DINPs, 3) the use of fucoidan (FC), a high affinity targeting ligand for P-selectin overexpressed on injured endothelium, to improve FC-DINPs attachment to the target site, and 4) the use of HA-DA, an adhesive hydrogel synthesized with hyaluronic acid (HA) and dopamine (DA), to mimic the adhesive strategies of blue mussels and to confer the characteristics needed to deliver FC-DINPs from the vehicle and gain adhesion to the inner blood vessel wall. Furthermore, this proposal focuses on promoting diversity, equity, inclusion, and accessibility (DEIA). Our proposed research approaches for the treatment of PAD are within the scope of the parent grant (“Novel nanoparticles to stimulate therapeutic angiogenesis in peripheral arterial disease”) and will help to foster the research career development of Ms. Ingrid D. Guerrero Rodriguez, a doctoral student from underrepresented minorities (URM) with a disadvantaged background and a physical disability. She will be mentored and supported by the PI, Dr. Kytai T. Nguyen, a researcher and educator with a proven record of her commitment to the advancement of minority students in STEM.

摘要 我们的父母补助金奖的长期目标是开发新的生物相容性和可生物降解的双模 成像纳米颗粒（DINPs），以提供细胞保护并促进应激下的治疗性血管生成 诸如外周动脉疾病（PAD）的局部缺血的病症。对于这一补充申请，我们建议 以下方法旨在丰富我们的母公司奖项的潜力：a）岩藻多糖（FC）的开发 具有优化的荧光和光声成像能力的靶向纳米颗粒（FC-DINPs），B） 用于同时经皮穿刺的FC-DINP负载的水凝胶血管成形术球囊涂层的制剂 c）评价FC-DINPs向离体血管成形术和局部药物递送的转移功效 猪的动脉节段。本设计的主要创新点是：1）同时成形术 通过贻贝激发的纳米复合材料球囊涂层进行治疗和局部递送治疗剂 通过FC-DINPs和粘性水凝胶的组合，以确保均匀和受控的药物 2）使用可生物降解的光致发光聚合物-苯胺四聚体（BPLPAT）来制备FC- DINPs，3）使用岩藻依聚糖（FC），一种高亲和力的P-选择素靶向配体，在损伤的 内皮，以改善FC-DINPs与靶部位的附着，以及4）使用HA-DA，一种粘附性水凝胶 用透明质酸（HA）和多巴胺（DA）合成，以模拟蓝贻贝的粘附策略， 赋予从溶媒中递送FC-DINP并粘附于内部血液所需的特性 血管壁此外，该提案侧重于促进多样性、公平、包容和无障碍。 我们提出的治疗PAD的研究方法在父母资助的范围内（“新颖的 纳米颗粒刺激外周动脉疾病的治疗性血管生成”），并将有助于促进 Ingrid D女士的研究职业发展。格雷罗罗德里格斯，一个博士生从代表性不足 （b）有残疾和身体残疾的少数民族。她将得到指导和支持 由PI Kytai T博士撰写。Nguyen是一位研究员和教育家，她致力于 少数民族学生在STEM方面的进步。