Enhancing Exosomal Delivery to Abdominal Aortic Aneurysms using Magnetically Responsive Chemotactic Nanomotors for Elastic Matrix Regenerative Repair

Abstract Abdominal aortic aneurysms (AAAs) involve localized dilation of the abdominal aorta, with the reversal of this condition being significantly limited by the inherently poor and abnormal regenerative repair of the aortic elastic matrix. Mesenchymal stem cell exosomes (MSCEs) are promising regenerative tools; however, achieving precise targeting of AAA with MSCEs is challenging owing to the high blood flow in the arterial system. In this study, an engineered exosomal nanomotor is developed for magnetic and chemical propulsion. The results demonstrate that this nanomotor effectively enhances the delivery of MSCEs to the AAA through magnetic field navigation and catalase‐induced chemotaxis. The nanomotor significantly enhances the elastic matrix repair, reduces oxidative stress, and activates the PI3K/Akt pathway, leading to aneurysm shrinkage and reversal. In addition, the nanomotor possesses magnetic resonance imaging capabilities. The use of this nanomotor offers a novel, targeted drug delivery system in a rat model of AAA and holds promise as a potential therapeutic option for this condition.