Multifunctional Microneedle Patches for Perivascular Gene Delivery and Treatment of Vascular Intimal Hyperplasia

Gene therapy has emerged as a promising approach to address challenging cardiovascular diseases. Extensive efforts have been focused on developing highly efficient gene vectors with precise delivery techniques to enhance its effectiveness. In this study, we present multifunctional dopamine-gelatin microneedle patches with gene therapy capabilities to achieve perivascular gene delivery for intimal hyperplasia treatment. These patches that were fabricated through freeze-drying of gelatin are with recombinant adeno-associated virus (rAAVs)-carrying tips and dopamine coating backing layers. The lyophilized gelatin could not only effectively preserve the therapeutic activity of rAAVs but could also demonstrate the capability to penetrate the adventitia for efficient delivery. The incorporation of dopamine facilitated patch adhesion and extended the release duration. Based on these advantages, we have demonstrated that the rAAVs-loaded microneedle patches (AMNPs) behave satisfactorily in perivascular gene delivery to inhibit carotid artery restenosis in rats. These features indicate that the AMNPs are clinically valuable in the treatment of vascular intimal hyperplasia diseases.基因治疗已成为应对棘手心血管疾病的极具前景的策略。学界已开展大量研究，致力于开发具备精准递送技术的高效基因载体，以提升基因治疗的疗效。本研究开发了一种兼具基因治疗功能的多功能多巴胺-明胶微针贴片，可实现血管周围基因递送，用于治疗内膜增生性疾病。该类贴片以明胶冷冻干燥法制备，其针尖负载重组腺相关病毒（recombinant adeno-associated virus, rAAVs），背衬层则涂覆多巴胺涂层。冻干明胶不仅可有效维持rAAVs的治疗活性，还可穿透血管外膜实现高效递送。多巴胺的掺入不仅提升了贴片的黏附性能，还延长了载体的释放周期。基于上述优势，本研究证实，负载rAAVs的微针贴片（rAAVs-loaded microneedle patches, AMNPs）可通过血管周围基因递送，有效抑制大鼠颈动脉再狭窄，表现出良好的治疗效果。上述特性表明，AMNPs在血管内膜增生性疾病的临床治疗中具有较高应用价值。