Udofot Ofonime, Lin Li-Hsien, Thiel William H, Erwin Megan, Turner Emily, Miller Francis J, Giangrande Paloma H, Yazdani Saami K
Internal Medicine, University of Iowa, Iowa City, IA, USA; Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA, USA.
Internal Medicine, University of Iowa, Iowa City, IA, USA.
Mol Ther Nucleic Acids. 2019 Jun 7;16:360-366. doi: 10.1016/j.omtn.2019.03.005. Epub 2019 Mar 23.
Current strategies to prevent restenosis following endovascular treatment include the local delivery of anti-proliferative agents to inhibit vascular smooth muscle cell (VSMC) proliferation and migration. These agents, not specific to VSMCs, are deposited on the luminal surface and therefore target endothelial cells and delay vascular healing. Cell-targeted therapies, (e.g., RNA aptamers), can potentially overcome these safety concerns by specifically binding to VSMC and inhibiting proliferation and migration. The purpose of this study was to therefore demonstrate the ability of a perfusion catheter to deliver cell-specific RNA aptamer inhibitors directly to the vessel wall. RNA aptamers specific to VSMCs were developed using an in vitro cell-based systematic evolution of ligand by exponential enrichment selection process. Two aptamers (Apt01 and Apt14) were evaluated ex vivo using harvested pig arteries in a pulsatile flow bioreactor. Local drug delivery of the aptamers into the medial wall was accomplished using a novel perfusion catheter. We demonstrated the feasibility to deliver aptamer-based drugs directly to the medial layer of an artery using a perfusion catheter. Such cell-specific targeted therapeutic drugs provide a potentially safer and more effective treatment option for patients with vascular disease.
目前，预防血管内治疗后再狭窄的策略包括局部递送抗增殖药物以抑制血管平滑肌细胞（VSMC）的增殖和迁移。这些药物并非VSMC特异性的，它们沉积在管腔表面，因此会作用于内皮细胞并延迟血管愈合。细胞靶向疗法（例如RNA适配体）通过特异性结合VSMC并抑制其增殖和迁移，有可能克服这些安全问题。因此，本研究的目的是证明灌注导管将细胞特异性RNA适配体抑制剂直接递送至血管壁的能力。通过基于体外细胞的指数富集配体系统进化筛选过程，开发了VSMC特异性的RNA适配体。使用收获的猪动脉在脉动流生物反应器中对两种适配体（Apt01和Apt14）进行了体外评估。使用新型灌注导管将适配体局部药物递送至中膜壁。我们证明了使用灌注导管将基于适配体的药物直接递送至动脉中膜层的可行性。这种细胞特异性靶向治疗药物为血管疾病患者提供了一种潜在更安全、更有效的治疗选择。
