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Current treatment options are limited, necessitating novel therapeutic approaches. This study investigates the potential of a pioneering nanodrug delivery system, RAP@PFB, in mitigating AAA progression. RAP@PFB integrates pentagalloyl glucose (PGG) and rapamycin (RAP) within a metal\u2013organic\u2010framework (MOF) structure through a facile assembly process, ensuring remarkable drug loading capacity and colloidal stability. The synergistic effects of PGG, a polyphenolic antioxidant, and RAP, an mTOR inhibitor, collectively regulate key players in AAA pathogenesis, such as macrophages and smooth muscle cells (SMCs). In macrophages, RAP@PFB efficiently scavenges various free radicals, suppresses inflammation, and promotes M1\u2010to\u2010M2 phenotype repolarization. In SMCs, it inhibits apoptosis and calcification, thereby stabilizing the extracellular matrix and reducing the risk of AAA rupture. Administered intravenously, RAP@PFB exhibits effective accumulation at the AAA site, demonstrating robust efficacy in reducing AAA progression through multiple mechanisms. Moreover, RAP@PFB demonstrates favorable biosafety profiles, supporting its potential translation into clinical applications for AAA therapy.<\/jats:p>","DOI":"10.1002\/smll.202402141","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T06:40:16Z","timestamp":1719902416000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Dual\u2010Drug Nanomedicine Assembly with Synergistic Anti\u2010Aneurysmal Effects via Inflammation Suppression and Extracellular Matrix Stabilization"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8028-7245","authenticated-orcid":false,"given":"Hong Lin","family":"Zu","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong 510120 China"},{"name":"The Key Laboratory of Advanced Interdisciplinary Studies The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei Pei","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Peng","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha Hunan 410013 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi Jia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing Shan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen Hu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences Central South University  Changsha Hunan 410013 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong 510120 China"},{"name":"The Key Laboratory of Advanced Interdisciplinary Studies The First Affiliated Hospital of Guangzhou Medical University  Guangzhou Guangdong 510120 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"e_1_2_8_1_1","first-page":"452","volume":"13","author":"Johnston K. 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