Novel nanoparticles to stimulate therapeutic angiogenesis in peripheral arterial disease

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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.