Targeted Catalytic Anti-Inflammatory and Antioxidant Therapy for Aortic Dissection Using Biomimetic Nanomaterials.

Aortic dissection (AD) is a life-threatening cardiovascular disease with an extremely high mortality rate. Excessive reactive oxygen species (ROS) production and inflammatory responses in diseased vascular regions are central drivers of AD pathogenesis, leading to destruction of the aortic wall structure and fatal hemorrhage. However, conventional clinical therapies for AD cannot effectively eliminate excessive ROS at lesion sites while simultaneously exerting anti-inflammatory effects. To address these limitations, we developed a biomimetic, inflammation-targeting nanoparticle, ZIF-8@Res@PEG-FA (ZRF), to attenuate AD progression through potent antioxidant and anti-inflammatory interventions. ZRF is constructed with ZIF-8 as the core carrier, loaded with the antioxidant and anti-inflammatory agent resveratrol, and surface-modified with PEG-folic acid (PEG-FA). This nanoparticle enhances resveratrol bioavailability and leverages the inflammation-targeting capability of folic acid to preferentially accumulate in AD lesions. Under mildly acidic conditions, ZRF rapidly degrades and efficiently scavenges ROS, disrupting the oxidative stress-inflammation vicious cycle and promoting the polarization of pro-inflammatory M1 macrophages toward the anti-inflammatory M2 phenotype. Notably, ZRF also preserves the contractile phenotype of vascular smooth muscle cells (VSMCs), maintains extracellular matrix stability, and thereby delays AD progression. This study presents a promising therapeutic strategy for aortic dissection and other inflammatory vascular diseases.