Abdominal aortic aneurysms (AAAs) remain a major public health concern, with limited treatment options beyond surgical intervention for large lesions. The absence of effective pharmacotherapies underscores the urgent need for innovative strategies that can halt or reverse disease progression in early stages. This study demonstrates that systemic administration of targeted nanoparticles loaded with pentagalloyl glucose (PGG) can effectively reverse angiotensin II (Ang II)-induced abdominal aortic aneurysms in mice, restoring vascular structure and function through precise drug delivery.
The therapeutic strategy leverages the pathological hallmark of AAA—elastin degradation—as a molecular target. We developed bovine serum albumin (BSA) nanoparticles conjugated with an anti-elastin antibody that selectively binds to fragmented elastin in the aneurysmal wall while avoiding intact elastic fibers. These nanoparticles were loaded with PGG, a natural polyphenol known for its ability to stabilize and regenerate elastic matrix components. In a well-established murine model, male LDL receptor-deficient (LDLr⁻/⁻) mice received subcutaneous osmotic pumps delivering Ang II over four weeks, inducing spontaneous aneurysm formation with histological and biomechanical features closely resembling human disease.ATG4C Antibody Formula
Following aneurysm induction, mice were treated with two intravenous injections of either PGG-conjugated nanoparticles (PGG-NPs) or blank nanoparticles (BLN-NPs) at weeks 4 and 6 post-infusion. Control animals received no treatment. Ultrasound monitoring revealed sustained dilation in control and BLN-NP groups, with mean aneurysmal diameters increasing from ~104% to over 180% of baseline by week 8. In contrast, the PGG-NP group exhibited a significant reversal in dilation, reducing the percentage increase from 139.16% to 97.75% (p < 0.05), indicating active regression of the aneurysm. Histopathological evaluation confirmed structural recovery. Hematoxylin and eosin (H&E) staining showed markedly reduced inflammatory cell infiltration in the adventitia and media of PGG-treated aortas. Verhoeff-van Gieson (VVG) staining revealed complete restoration of elastic laminae, a feature absent in controls. In-situ zymography demonstrated suppressed MMP activity in the PGG-NP group, correlating with qPCR results showing downregulation of MMP-2 and upregulation of tissue inhibitors TIMP-1 and TIMP-2—indicating a rebalancing of proteolytic homeostasis. Beyond morphological improvement, functional recovery was evident. Circumferential strain (CS) analysis indicated that PGG-treated aortas regained distensibility, with CS reduction decreasing from ~78% in controls to only ~24.TCEA1 Antibody supplier 5% in the PGG group (p < 0.05). Pulse wave velocity (PWV), a marker of arterial stiffness, also improved significantly—rising from 0.97 mm/ms in untreated controls to 2.43 mm/ms in the PGG group (p < 0.05), approaching levels seen in healthy aortas. Systemic inflammation markers further supported therapeutic efficacy. Serum IFN-γ levels were lowest in the PGG-NP group (13.PMID:35127167 55 ± 8.09 pg/mL), significantly lower than both control (49.94 ± 14.30 pg/mL) and BLN-NP (33.34 ± 13.16 pg/mL) groups (p < 0.01). Flow cytometry confirmed reduced CD68-positive macrophage populations in the spleen, suggesting diminished systemic immune activation. Ex vivo biomechanical testing validated these findings. At 100 mmHg pressure, PGG-treated vessels showed significantly smaller outer diameters and greater mid-wall circumferential stretch compared to controls. Tangential stiffness was markedly reduced, especially at low stretch ratios (1.1), indicating enhanced elasticity consistent with elastin repair. These results demonstrate that targeted PGG delivery not only reverses structural damage but also restores physiological mechanical behavior. This study establishes that systemic nanoparticle delivery of PGG via elastin-targeting antibodies can effectively reverse established AAAs in mice. By combining precise targeting, ECM stabilization, and anti-inflammatory effects, this approach addresses multiple facets of AAA pathophysiology. It presents a viable, non-invasive alternative for patients with small or moderate aneurysms who are currently ineligible for medical therapy. Future clinical translation may offer a transformative strategy for preventing rupture and improving long-term outcomes in AAA patients.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com