Aortic dissection/aneurysm (AAD) is a critical and life-threatening condition marked by a lack of effective pharmacological treatments. Gene therapy has emerged as a promising approach to treat AAD and slow its advancement. However, the clinical utility of gene therapy is impeded by significant challenges, including the scarcity of innovative genetic drugs in current medical practices and the absence of a streamlined gene delivery mechanism. Our investigation centered on a unique gene target, tRF-Gly-CCC, belonging to tsRNAs, essential for maintaining vascular smooth muscle cell function and regulating inflammatory cell responses. To enhance in vivo treatment, we developed a kind of activated neutrophil membrane bionic nanoparticles (neu MCs), incorporating tRF-Gly-CCC-loaded polymer nanoparticles as the core and activated neutrophil membrane as the outer layer. The utilization of activated neutrophil membrane cloaking serves a dual purpose by safeguarding tRF-Gly-CCC and facilitating targeted delivery to the AAD site. Neu MCs exhibit improved stability in circulation, enabling precise delivery to aortic lesions and reducing AAD mortality. Notably, studies suggest that neu MCs offer a superior approach for immediate intervention to reduce vascular rupture. In conclusion, our study utilized a novel genetic drug and an effective delivery system to enable early intervention in AAD.

中文翻译：

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活化的中性粒细胞膜包被的 tRF-Gly-CCC 纳米颗粒用于治疗主动脉夹层/动脉瘤


主动脉夹层/动脉瘤 （AAD） 是一种严重且危及生命的疾病，其特点是缺乏有效的药物治疗。基因疗法已成为治疗 AAD 并减缓其发展的一种有前途的方法。然而，基因治疗的临床应用受到重大挑战的阻碍，包括当前医疗实践中创新基因药物的稀缺以及缺乏简化的基因递送机制。我们的研究集中在一个独特的基因靶点 tRF-Gly-CCC 上，它属于 tsRNA，对维持血管平滑肌细胞功能和调节炎症细胞反应至关重要。为了增强体内处理，我们开发了一种活化的中性粒细胞膜仿生纳米颗粒 （neu MCs），以载有 tRF-Gly-CCC 的聚合物纳米颗粒为核心，活化的中性粒细胞膜为外层。活化的中性粒细胞膜隐身的利用具有双重目的，即保护 tRF-Gly-CCC 并促进靶向递送至 AAD 位点。Neu MC 表现出更好的循环稳定性，能够精确输送到主动脉病变并降低 AAD 死亡率。值得注意的是，研究表明，neu MCs 提供了一种更好的立即干预以减少血管破裂的方法。总之，我们的研究利用一种新型遗传药物和有效的递送系统来实现 AAD 的早期干预。