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

Abstract

To address the therapy need of abdominal aortic aneurysm (AAA), a targeting modified multifunctional nano-delivery system (rCT-AuM) was developed, including the Au nanorod-cluster@mesoporous polydopamine core with the 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 the cell phenotype under NIR-II, and demonstrated the potential to promote endothelial repair. In an AAA mouse model, rCT-AuM exhibited significant lesion targeting and 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.