Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice

Abstract

Abdominal aortic aneurysm (AAA) disease causes dilation of the aorta, leading to aortic rupture and death if not treated early. It is the 14th leading cause of death in the U.S. and 10th leading cause of death in men over age 55, affecting thousands of patients. Despite the prevalence of AAA, no safe and efficient pharmacotherapies exist for patients. The deterioration of the elastic lamina in the aneurysmal wall is a consistent feature of AAAs, making it an ideal target for delivering drugs to the AAA site. In this research, we conjugated nanoparticles with an elastin antibody that only targets degraded elastin while sparing healthy elastin. After induction of aneurysm by 4-week infusion of angiotensin II (Ang II), two biweekly intravenous injections of pentagalloyl glucose (PGG)-loaded nanoparticles conjugated with elastin antibody delivered the drug to the aneurysm site. We show that targeted delivery of PGG could reverse the aortic dilation, ameliorate the inflammation, restore the elastic lamina, and improve the mechanical properties of the aorta at the AAA site. Therefore, simple iv therapy of PGG loaded nanoparticles can be an effective treatment option for early to middle stage aneurysms to reverse disease progression and return the aorta to normal homeostasis.

Pentagalloyl Glucose, a Major Compound in Mango Seed Kernel, Exhibits Distinct Gastroprotective Effects in Indomethacin-Induced Gastropathy in Rats via Modulating the NO/eNOS/iNOS Signaling Pathway

“…Moreover, in LPS-stimulated RAW 264.7 cells, PGG dramatically reduced secretions of TNF-α, IL-1, IL-6, and NO ( Zhang et al, 2021 ). Furthermore, in accordance with the present study, in vivo studies on the animal model of aortic aneurysm showed that PGG nanoparticles suppressed inflammatory cell infiltration and systemic inflammation ( Wang et al, 2021 ).…”

Cornu aspersum mucin attenuates indomethacin-induced gastric ulcers in mice via alleviating oxidative stress and inflammation

“…ROS generated in gastric tissues by activated neutrophils was associated with delayed stomach ulcer healing [ 53 ]. Intracellular antioxidants such as catalase and GSH could neutralize the generated ROS [ 54 ].…”

Treatment With Small Molecule Inhibitors of Advanced Glycation End‐Products Formation and Advanced Glycation End‐Products‐Mediated Collagen Cross‐Linking Promotes Experimental Aortic Aneurysm Progression in Diabetic Mice

“… 62 Systemic delivery of nanoparticle‐conjugated antielastin antibodies also suppressed angiotensin II‐induced AAA progression. 63 These complementary results lend further support to the concept of enhanced ECM proteolytic resistance as a viable AAA suppression strategy.…”