Xu Yiyan, Wang Ying, Guan Li, Zhang Peng, Wu Zhen, Jehan Shah, Peng Chao, Yang Bohan, Yao Ye, Zhuang Peipei, Zhou Wenhu, Zhang Wayne W, Wang Haiyang
Department of Vascular Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China.
Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China.
ACS Appl Mater Interfaces. 2025 Jun 18;17(24):35080-35098. doi: 10.1021/acsami.5c03008. Epub 2025 Jun 6.
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.
腹主动脉瘤（AAA）因有破裂风险而构成严重且紧迫的威胁，是一种危及生命的情况。尽管情况紧急，但目前缺乏有效的临床药物来抑制动脉瘤生长并预防破裂。针对AAA病变固有的复杂病理变化，本项目引入了一种多功能纳米药物，利用茶多酚纳米颗粒作为载体，将多西环素（DC）特异性靶向至AAA。通过巯基聚乙二醇-环肽（SH-PEG-cRGD）修饰，纳米颗粒（NPs）在AAA病变处的蓄积量显著增加了5倍，通过识别病变细胞膜上过度表达的整合素αvβ3受体实现精准递送。这种纳米药物在活性氧（ROS）水平升高触发下于AAA部位实现DC的可控释放，这与纳米载体固有的抗氧化能力协同作用。其综合作用包括抗炎、抗氧化、巨噬细胞极化、抗凋亡和抗钙化能力，以及基质金属蛋白酶（MMP）抑制，有效解决了与AAA相关的各种病理变化及治疗问题。值得注意的是，纳米载体递送显著减轻了DC诱导的肝毒性和肾毒性，凸显了其卓越的生物相容性。本研究提出了一种具有巨大动脉瘤治疗潜力的靶向纳米药物，并为各种血管疾病靶向药物的开发提供了蓝本。
