Precision Drug Delivery for Multifunctional Treatment of Abdominal Aortic Aneurysm Using Bioactive Tea Polyphenol...

Abdominal aortic aneurysm (AAA) poses a critical and imminent threat due to the potential for rupture, presenting a life-threatening scenario. Despite the urgency, there is a lack of an effective clinical drug to impede aneurysm growth and prevent rupture. Addressing the intricate pathological changes inherent in AAA lesions, this project introduces a multifunctional nanomedicine utilizing tea polyphenol nanoparticles as carriers for doxycycline (DC) targeted specifically to AAA. Through SH-PEG-cRGD modification, the nanoparticles (NPs) demonstrate a remarkable 5-fold increase in accumulation at AAA lesions, achieving precise delivery by recognizing the overexpressed integrin αvβ3 receptors on lesion cell membranes. This nanomedicine achieves controlled DC release at the AAA site triggered by elevated reactive oxygen species (ROS) levels, which synergizes with the inherent antioxidant prowess of the nanocarrier. The combined effect encompasses anti-inflammatory, antioxidant, macrophage repolarization, antiapoptotic, and anticalcification capabilities, along with matrix metalloproteinase (MMP) inhibition, effectively addressing diverse AAA-associated pathological changes and therapy. Notably, nanocarrier delivery significantly mitigates the hepatic and renal toxicity induced by DC, highlighting exceptional biocompatibility. This study propounds a targeted nanomedicine with substantial potential for aneurysm treatment and serves as a blueprint for the development of targeted drugs for various vascular diseases.