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.

抽象的 我们的家长资助奖的长期目标是开发新型生物相容性和可生物降解的双模式 成像纳米粒子（DINP）提供细胞保护并促进应激下的治疗性血管生成 外周动脉疾病（PAD）引起的缺血等疾病。对于此补充申请，我们建议 以下方法旨在丰富我们母奖的潜力：a) 岩藻依聚糖 (FC) 的开发 具有优化的荧光和光声成像能力的靶向纳米粒子（FC-DINP），b） 用于同步经皮的负载 FC-DINP 的水凝胶血管成形球囊涂层的配方 腔内血管成形术和局部药物递送，以及 c) FC-DINP 体外转移功效的评估 猪动脉的片段。我们设计的主要创新点是：1）同步血管成形术 通过形成的受贻贝启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-DINP 和粘性水凝胶的结合，以确保均匀且受控的药物 交付，2）使用可生物降解的光致发光聚合物苯胺四聚体（BPLPAT）来制造FC- DINP，3) 使用岩藻依聚糖 (FC)，这是一种高亲和力靶向配体，用于在损伤部位过表达的 P-选择素 内皮细胞，以改善 FC-DINP 对目标位点的附着，以及 4) 使用 HA-DA（一种粘性水凝胶） 由透明质酸 (HA) 和多巴胺 (DA) 合成，模仿蓝贻贝的粘附策略 赋予从载体输送 FC-DINP 所需的特性并获得对内部血液的粘附 血管壁。此外，该提案的重点是促进多样性、公平性、包容性和可及性（DEIA）。 我们提出的治疗 PAD 的研究方法属于母基金的范围（“Novel 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 来自弱势群体的博士生 Ingrid D. Guerrero Rodriguez 女士的研究职业发展 具有弱势背景和身体残疾的少数群体 (URM)。她将得到指导和支持 由 PI Kytai T. Nguyen 博士负责，她是一位研究员和教育家，她对 少数民族学生在 STEM 方面的进步。