Graduation Semester and Year
Summer 2026
Language
English
Document Type
Dissertation
Degree Name
Doctor of Philosophy in Biomedical Engineering
Department
Bioengineering
First Advisor
Dr. Kytai T. Nguyen
Second Advisor
Dr. Juhyun Lee
Third Advisor
Dr. Tam Nguyen
Fourth Advisor
Dr. Liping Tang
Fifth Advisor
Dr. Pan Zui
Abstract
Peripheral artery disease (PAD) restricts blood flow in the arteries, causing limb ischemia and high morbidity. Current treatments include invasive surgical revascularization or medications that mainly relieve symptoms without addressing the underlying cause. However, many older patients with PAD are not suitable candidates for surgery, highlighting the need for alternative therapies. To address this, we developed cyclo(1,12)-PenITDGEATDSGC (cLABL) targeted multifunctional nanoparticles (MNPs) loaded with erythropoietin and its plasmid for localized, ICAM-1-targeted delivery to ischemic tissue (cLABL/E/cE MNPs). These MNPs also enable fluorescent and photoacoustic imaging to track nanoparticles biodistribution. The ~240 nm theranostic cLABL/E/cE MNPs nearly doubled cellular uptake in vitro and showed 1.5-fold higher localization at 2 hours and 3.6-fold higher at 7 days post-injection in PAD mice. They enabled fluorescence and photoacoustic imaging for biodistribution tracking in vitro and in vivo. The cLABL/E/cE NPs outperformed single-loaded formulations, increasing proliferation by 27%, migration by 20%, and tube formation by over twofold. In PAD mice, the cLABL/E/cE MNPs restored blood perfusion significantly higher than free treatment, while saline and blank controls showed no improvement. Histology confirmed at least 2.5-fold reductions in inflammation, adipocyte infiltration, and fibrosis, along with 2-fold greater neovascularization. The MNPs were safe across different cells lines and red blood cells, as well as other organs in the PAD model, showing no differences in toxicity across groups. Overall, our targeted cLABL/E/cE MNPs prevented apoptosis, enhanced angiogenesis, restored perfusion, and enabled real-time imaging, offering a promising alternative therapy for PAD.
Keywords
Peripheral artery disease, Nanoparticles, Erythropoietin, Gene delivery, Protein delivery, cLABL, Theranostics, Photoacoustic imaging, Fluorescence imaging
Disciplines
Biomedical Engineering and Bioengineering | Biotechnology | Nanoscience and Nanotechnology
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Nguyen, Na Thi Vy, "Engineering Targeted Nanoparticles to Enable Imaging and Therapeutic Angiogenesis in Peripheral Arterial Disease" (2026). Bioengineering Dissertations. 5.
https://mavmatrix.uta.edu/bioengineering_dissertations2/5
Included in
Biomedical Engineering and Bioengineering Commons, Biotechnology Commons, Nanoscience and Nanotechnology Commons