Nanomaterial interventions in abdominal aortic aneurysm (AAA): From microenvironment modulation to vascular reconstruction.

Abdominal aortic aneurysm (AAA) is a common vascular disease among the elderly with considerable mortality risk. Current therapeutic strategies, such as open surgical repair and endovascular repair, primarily reduce rupture risk by mechanically excluding the aneurysm but have limited effects on the underlying inflammation and structural deterioration of the aortic wall. Nanomaterials, with their tunable structures and microenvironment-responsive properties, offer new opportunities for precise intervention and vascular reconstruction. This review focuses on the pathological microenvironment of AAA, detailing key processes such as inflammatory and immune imbalance, extracellular matrix degradation, protease network activation, and oxidative stress, and maps out potential therapeutic targets. It summarizes advances in polymer-based, inorganic, and biomimetic nanoplatforms for drug delivery, targeting proteases and reactive oxygen species, local anti-inflammatory and immunomodulation, as well as mechanical reinforcement and tissue repair using biomimetic extracellular matrix nanofibers, hydrogels, or stent nanocoatings. The value and limitations of ultrasmall superparamagnetic iron oxide contrast agents and theranostic nanoplatforms for imaging-based assessment and monitoring are also discussed. Two technical pathways are highlighted: lesion-microenvironment-guided targeted nanotherapy and intelligent vascular repair through microenvironment remodeling. The review emphasizes shifting treatment goals from merely controlling aneurysm expansion to restoring arterial wall structure and function, while acknowledging ongoing challenges in safety evaluation, scalable manufacturing, and clinical integration. Overall, pathological microenvironment-based nanotheranostic strategies show promising potential to modulate disease progression, promote vascular repair, improve risk assessment, and enable more individualized long-term management of AAA.