Background: Elastin degradation is a defining feature of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) progression. Previous work demonstrated that elastin-targeted entagalloyl glucose nanoparticles (PGG-NPs) reverse established elastase-induced and AngII-induced AAA by reducing inflammation while preserving the extracellular matrix. Whether PGG-NPs is effective in rupture prone AngII-BAPN model characterized by TAA and AAA formation, spontaneous aortic rupture and increased mortality has not been determined. Methods: ApoE?/? mice received continuous angiotensin II (AngII) infusion (1,500 ng kg-¹ min-¹) and 0.2% ?-aminopropionitrile (BAPN) in drinking water to induce TAA or AAA. PGG-NPs (10 mg kg-¹) or Blank-NPs were administered intravenously twice weekly. Gross morphology, Kaplan–Meier survival, aneurysm incidence, histology and ?-smooth muscle actin (?SMA) expressions were evaluated after 28 days. Results: AngII-BAPN induced aneurysm formation in both thoracic and abdominal aortic segments with increased mortality. PGG-NPs treatment significantly improved survival compared with Blank-NP-treated mice (log-rank, P = 0.0132). Gross and histological analyses demonstrated reduced aneurysmal remodeling, decreased pathological medial thickening and enhanced ?SMA expression following PGG treatment. AAA incidence was significantly reduced from 75.0% in Blank-NP-treated mice to 23.1% in PGG-treated mice (Fisher’s exact test, P = 0.0092). TAA incidence also decreased from 25.0% to 15.4%, although this difference was not statistically significant (P = 0.663). Conclusions: PGG-NPs reduce aneurysm burden and improve survival in the AngII-BAPN model while maintaining elastic fiber architecture and vascular smooth muscle integrity. Extension of therapeutic efficacy in ANGII-BAPN model involving both TAA and AAA further supports PGG stabilization of degraded elastin as a promising therapeutic target for aortic aneurysm disease.