Diagnosis, Rupture Risk Evaluation and Therapeutic Intervention of Abdominal Aortic Aneurysms Using Targeted Nanoparticles
Date of Award
Doctor of Philosophy (PhD)
Jeoung Soo Lee
Abdominal aortic aneurysm (AAA) disease causes dilation of the aorta that can lead to aortic rupture and death if not treated early. It is the 14th leading cause of death in the U.S. and is cited as the 10th leading cause of death in men over age 55, affecting thousands of patients and their families. To date, AAA patients have minimal access to safe and efficient imaging modalities for diagnosis as well as pharmacotherapies. AAA is usually detected and monitored with ultrasonography or contrast-enhanced computed tomography (C.T.), which doesn’t provide biomechanical information of the AAAs that are essential for predicting rupture risks. Furthermore, unfortunately, there is no currently known pharmaceutical treatment to cure the AAAs.
Key pathological processes occurring within AAAs include inflammation, vascular smooth muscle cell apoptosis, and extracellular matrix (ECM) degradation. The deterioration of the elastic lamina in the aneurysmal wall is a consistent feature of AAAs and the fact that the adult elastic lamina does not remodel in aneurysm progression, making it an ideal target for delivering contrast agents and treatments. In this research, we have delivered gold nanoparticles (AuNPs), a commonly used C.T. contrast agent, and pentagalloyl glucose (PGG) loaded nanoparticles to the AAAs in an angiotensin II (AngII) infusion induced mouse model by conjugating the nanoparticles with antibodies that target degraded elastin.
Here, owing to their degraded elastin targeting ability, we have observed a positive correlation between the quantities of the locally accumulated AuNPs in the aneurysmal tissue in C.T. scans and the elastin damage levels of the AAAs. Furthermore, the AuNPs accumulations were found negatively correlated to the mechanical properties of the AAAs, which makes AuNPs a potential non-invasive surrogate marker of AAA rupture risk. Moreover, we have shown that targeted delivery of PGG could reverse the aortic dilation, ameliorate the inflammation, restore the elastin as well as the AAA mechanical properties of the aneurysmal tissue. Therefore, PGG loaded nanoparticles can be an effective treatment option for early to middle stage aneurysms to prevent disease progression.
Wang, Xiaoying, "Diagnosis, Rupture Risk Evaluation and Therapeutic Intervention of Abdominal Aortic Aneurysms Using Targeted Nanoparticles" (2020). All Dissertations. 2672.