DOI: 10.1161/circ.148.suppl_1.12931 ISSN: 0009-7322

Abstract 12931: Development of Novel Targeted, Membrane-Coated Polymer Hybrid Nanoparticles for Endothelial Repair Following Balloon Angioplasty in Rat Carotid Artery Model

Lalithasri Ramasubramanian, Nataliya Bahatyrevich, Dake Hao, Christopher Pivetti, Emma G Loll, Zachary J Paxton, Siraj S Gidda, Priyadarsi Kumar, Diana L Farmer, Alyssa Panitch, Aijun Wang
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Background: Coronary and peripheral arterial disease remains one of the leading causes of death worldwide. Treatments include balloon angioplasty, stent placement, or bypass grafting, all of which damage the endothelium and increase the risk of thrombosis or intimal hyperplasia. Thus, there is a critical need for rapid reendothelialization following these treatments. Endothelial progenitor cell-derived (EPC) extracellular vesicles (EVs) containing proangiogenic microRNAs, such as miR126, is one of the natural mechanisms of vascular repair. However, the translational application of EVs is limited by low EV yield, functional heterogeneity, and difficult tissue targeting.

Hypothesis: We hypothesize that EV-inspired hybrid nanoparticles can improve reendothelialization and modification with a specific collagen binding peptide SILY can target vascular injury.

Aims: (1) Engineer and characterize a SILY modified hybrid EPC membrane coated nanoparticles (SILY-ENPs) containing a miRNA-126-loaded poly-lactic-co-glycolic acid core (miR126-PLGA) in vitro . (2) Test the therapeutic efficacy of the SILY-ENPs in an in vivo rat carotid balloon angioplasty model.

Methods: EPC plasma membranes were isolated from umbilical cord blood EPCs and conjugated with SILY using copper-free Click chemistry. Membrane fragments were coextruded with miR126-PLGA to form SILY-ENPs. Particles were characterized in vitro for collagen and platelet binding and angiogenic function. In vivo function was tested in a rat carotid balloon angioplasty model.

Results: SILY-ENPs were found to have increased collagen binding and decreased platelet activity. Delivery of miR126 cargo slightly improved pro-angiogenic protein expression and increased rates of reendothelialization. However, SILY-ENPs were found to stimulate hyperplasia as an adverse side-effect.

Conclusions: SILY-ENPs exhibited target specificity, decreased platelet activity, and increased rates of reendothelialization, but increased intimal hyperplasia. This technology represents a novel EV inspired nanoplatform which can be tailored for treating various diseases by altering the cargo or membrane coating.

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