ORCID Identifier(s)

0000-0002-5282-4285

Graduation Semester and Year

2020

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering

Department

Bioengineering

First Advisor

Liping Tang

Abstract

Percutaneous coronary intervention (PCI) such as balloon angioplasty and stent placement are commonly employed for myocardial revascularization. These strategies, however, injure the arterial wall initiating a cascade of inflammatory responses that culminates in restenosis. Attempts are currently being made to improve the stents/balloon designs such that they suppress the inflammatory responses and support/enhance in situ reendothelialization. But the healing of the injured artery remains a major challenge. Therefore, in this work, we propose to characterize and identify a suitable fluorescent nanoparticle system that has potential to be used as vascular drug carriers. We also developed nanoparticles (NPs) that could enhance homing of more endothelial cells towards the injured arterial wall and facilitate their retention at that site, thereby promoting accelerated reendothelialization. In the first approach, biodegradable photo-luminescent polylactone (BPLP) copolymers such as BPLP-co-poly (L-lactide) (BPLP-PLLA) and BPLP-co-poly(lactic-co-glycolic) acid (BPLP-PLGA50:50 and BPLP-PLGA75:25), that have intrinsic fluorescent properties were utilized to prepare fluorescent nanoparticles. These NPs would allow us to not only track their location following transplantation, but to also estimate the required dosing for administering and to assess the therapeutic outcome. Based on physical and in vitro compatibility properties of these investigated NPs, BPLP-PLGA NPs demonstrated as optimal fluorescent NPs with potential to be utilized for diagnosis and treatment of cardiovascular diseases. In the second approach, we created a nanoparticle system that enabled fast capture of endothelial cells by incorporating highly selective biorthogonal click chemistry between tetrazines and transcyclooctene. Our strategy of pre-targeting tetrazine modified nanoparticles demonstrates the specific binding of these NPs onto the injured arterial wall and then capturing and retaining transcyclooctene modified endothelial cells to promote faster vascular healing. Taken together, these two approaches have outstanding potential applications in the detection and treatment of cardiovascular diseases.

Keywords

Percutaneous coronary intervention, endothelialization, fluorescent nanoparticle, biorthogonal click chemistry cardiovascular diseases

Disciplines

Biomedical Engineering and Bioengineering | Engineering

Comments

Degree granted by The University of Texas at Arlington

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