Enhanced Vascular Smooth Muscle Cell and Extracellular Matrix Repair Using a Metal‐Organic Framework‐Based Co‐Delivery System for Abdominal Aortic Aneurysm Therapy

Abstract The abdominal aortic aneurysm (AAA) is a severe and complex condition characterized by the pathological dilation of the abdominal aorta. Current therapeutic strategies are limited, with surgical repair being the most effective intervention due to the lack of medications that can slow aneurysmal expansion or prevent adverse events. In this study, an innovative nanoplatform, Mn‐UiO‐66‐NH 2 @HA, designed to repair vascular smooth muscle cells (VSMCs), and the extracellular matrix (ECM) is developed, thereby enhancing arterial wall integrity. This nanoplatform utilizes the classic metal‐organic framework (MOF) UiO‐66‐NH 2 , doped with manganese ions (Mn 2+ ) and coated with hyaluronate tetrasaccharide (4‐mer HA). The Mn‐UiO‐66‐NH 2 @HA nanoparticles demonstrates excellent drug‐loading efficiency, sustained release properties, and biocompatibility. In vitro, these nanoparticles significantly increases VSMC contractility and up‐regulated elastin and lysyl oxidase expressions, crucial for ECM repair, while inhibiting matrix metalloproteinases. In vivo studies on an Ang II‐induced AAA mouse model reveals that Mn‐UiO‐66‐NH 2 @HA effectively reduces aneurysmal expansion and improves aortic structural integrity. This study presents a promising co‐delivery system leveraging MOF carriers coated with 4‐mer HA and Mn 2+ , offering a novel therapeutic strategy for the treatment and management of AAA.