Li Dongyan, Ji Jing, Li Xinyue, Xie Yi, Huang Yan, Qin Junzhi, Ding Xili, Wang Lizhen, Fan Yubo
Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China.
School of Engineering Medicine, Beihang University, Beijing, Beijing, 100191, China.
Mater Today Bio. 2025 Mar 22;32:101695. doi: 10.1016/j.mtbio.2025.101695. eCollection 2025 Jun.
Severe corneal injuries often result in corneal scarring, leading to visual impairment and corneal blindness. Currently, there is a lack of effective anti-corneal fibrosis drugs in clinical practice. MicroRNA-based therapies hold significant potential in combating fibrosis. However, the barrier function of the cornea and the fluid environment of the ocular surface reduce drug permeability and bioavailability, presenting significant challenges for local drug application. This study employs microfluidic technology to encapsulate miRNA29b in lipid nanoparticles (LNP) to create an LNP-miRNA29b delivery system (LNP-mir29b) for treating corneal mechanical injuries. experiments show that LNP-mir29b significantly inhibits the expression of α-smooth muscle actin (α-SMA) in an induced corneal stromal cell fibrosis model. experiments using rabbit corneal mechanical injury models indicate that LNP-mir29b effectively reduces fibrosis in the corneal stroma, promotes organized rearrangement of stromal collagen fibers, and decreases the expression of fibrosis-related genes, including Col1A2, Col3A1, Fn, and α-SMA. Additionally, LNP-mir29b accelerates the migration of corneal epithelial cells, promotes wound healing of the epithelium, restores the structural integrity of the corneal epithelium. The LNP system proposed in this study offers a novel approach with anti-fibrotic functionality, providing a new strategy for reducing scarring during the corneal injury repair process.
严重的角膜损伤常导致角膜瘢痕形成,进而导致视力损害和角膜盲。目前,临床实践中缺乏有效的抗角膜纤维化药物。基于微小RNA的疗法在对抗纤维化方面具有巨大潜力。然而,角膜的屏障功能和眼表的液体环境降低了药物的通透性和生物利用度,给局部药物应用带来了重大挑战。本研究采用微流控技术将miRNA29b包裹在脂质纳米颗粒(LNP)中,以创建用于治疗角膜机械性损伤的LNP-miRNA29b递送系统(LNP-mir29b)。实验表明,在诱导的角膜基质细胞纤维化模型中,LNP-mir29b显著抑制α-平滑肌肌动蛋白(α-SMA)的表达。使用兔角膜机械性损伤模型的实验表明,LNP-mir29b有效减少角膜基质中的纤维化,促进基质胶原纤维的有序重排,并降低包括Col1A2、Col3A1、Fn和α-SMA在内的纤维化相关基因的表达。此外,LNP-mir29b加速角膜上皮细胞的迁移,促进上皮伤口愈合,恢复角膜上皮的结构完整性。本研究提出的LNP系统提供了一种具有抗纤维化功能的新方法,为减少角膜损伤修复过程中的瘢痕形成提供了新策略。