Construction of two drug-loaded gold nanoclusters@mesoporous polydopamine nanospheres and their synergistic treatment of abdominal aortic aneurysms

Abstract

To address therapy-need of abdominal aortic aneurysm (AAA), a targeting modified multifunctional nano delivery system (rCT AuM) was developed, including Au nanorod-cluster@mesoporous polydopamine core with c(RGDfK) targeting peptide and the active herbal ingredients tetramethylpyrazine (TMP) and cryptotanshinone (CTS). rCT AuM exhibited uniform mesopores, better NIR II photothermal conversion (efficiency 30.6%), and NIR-II responsive drug-release behavior. In cell experiments, rCT AuM could specifically target M1 macrophages and synthetic VSMCs, and through a photothermal chemotherapeutic synergy, effectively inhibited inflammation, modulated cell phenotype under NIR II, and demonstrated the potential to promote endothelial repair. In AAA mouse model, rCT AuM exhibited significant lesion targeting & accumulation; under NIR II irradiation, rCT AuM simultaneously achieved localized photothermal therapy and controlled release of TMP and CTS drugs, thereby effectively inhibiting aortic dilation, improving vascular elasticity, and restoring hemodynamic parameters. These results demonstrate that rCT-AuM can serve as a synergistic platform integrating active targeting, photothermal therapy, and chemotherapy, offering a new strategy for the precise treatment of AAA and providing novel insights for the management of aortic aneurysms.