Key Laboratory of Basic and Clinical Research of Heilongjiang Province, Eye Hospital, First Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, 150000, China.
Adv Healthc Mater. 2024 Jul;13(19):e2304381. doi: 10.1002/adhm.202304381. Epub 2024 May 11.
Corneal injury occurs frequently which may lead to serious visual impairment. Rapid and efficient re-epithelialization after corneal epithelial injury is the key issue for maintaining corneal homeostasis. Among various treatment strategies, microRNA (miR)-based therapy shows great potential. However, structural limitations of miRNAs hinder its biomedical functionality. Nucleic acid nanotechnology is an appealing candidate for gene delivery because of its flexible modification and excellent biocompatibility. Herein, modified 3D tetrahedral framework nucleic acids (tFNAs) utilized as gene carriers for miR-21 delivery are constructed. TFNAs-miR-21 (T-21) shows great enzymatic resistance in extracellular environment and payload delivery into human corneal epithelial cells (HCECs) via clathrin-mediated endocytosis. T-21 facilitates proliferation and migration in HCECs via activating PI3K/AKT and ERK1/2 signaling pathways in vitro. In vivo studies, T-21 can be internalized by corneal epithelium in mice. In the mice corneal scratch model, T-21 ophthalmic solutions used as eye drops show no apparent side effects on the ocular surface histologically and exert great potential in accelerating corneal wound healing. These findings demonstrate that modified tFNAs are promising candidates for miRNA delivery for corneal wound healing. The convenient administration and great biocompatibility of tetrahedral DNA nanoparticles highlight its potential as gene transporter in solving ocular problems.
角膜损伤很常见，可能导致严重的视力障碍。角膜上皮损伤后快速有效的再上皮化是维持角膜内稳态的关键。在各种治疗策略中，基于 microRNA（miR）的治疗方法显示出巨大的潜力。然而，miRNA 的结构限制阻碍了其生物医学功能。核酸纳米技术因其灵活的修饰和优异的生物相容性而成为基因递送的理想候选者。本文构建了用作 miR-21 递送载体的修饰的 3D 四面体型框架核酸（tFNAs）。TFNAs-miR-21（T-21）在细胞外环境中具有很强的酶抗性，并通过网格蛋白介导的内吞作用将有效载荷递送至人角膜上皮细胞（HCEC）。T-21 通过激活 PI3K/AKT 和 ERK1/2 信号通路在体外促进 HCEC 的增殖和迁移。在体内研究中，T-21 可以被小鼠角膜上皮内化。在小鼠角膜划痕模型中，T-21 眼用溶液作为滴眼液使用时，对眼表组织学没有明显的副作用，在加速角膜伤口愈合方面显示出巨大的潜力。这些发现表明，修饰的 tFNAs 是用于角膜伤口愈合的 miR 递送的有前途的候选物。四面体 DNA 纳米颗粒的给药方便和良好的生物相容性突出了其作为解决眼部问题的基因转运体的潜力。
