Activated neutrophil membrane-coated tRF-Gly-CCC nanoparticles for the treatment of aortic dissection/aneurysm.

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.