Wang Junyi, Calvert Andrea E, Kaplan Nihal, McMahon Kaylin M, Yang Wending, Lu Kurt Q, Peng Han, Thaxton C Shad, Lavker Robert M
Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Department of Ophthalmology, The Third Medical Center of Chinese PLA General Hospital, Beijing, China.
Adv Ther (Weinh). 2020 Dec;3(12). doi: 10.1002/adtp.202000138. Epub 2020 Sep 30.
microRNAs regulate numerous biological processes, making them potential therapeutic agents. Problems with delivery and stability of these molecules have limited their usefulness as treatments. We demonstrate that synthetic high-density lipoprotein nanoparticles (HDL NPs) topically applied to the intact ocular surface are taken up by epithelial and stromal cells. microRNAs complexed to HDL NPs (miR-HDL NPs) are similarly taken up by cells and tissues and retain biological activity. Topical treatment of diabetic mice with either HDL NPs or miR-HDL NPs significantly improved corneal re-epithelialization following wounding compared with controls. Mouse corneas with alkali burn-induced inflammation, topically treated with HDL NPs, displayed clinical, morphological and immunological improvement. These results should yield a novel HDL NP-based eye drop for patients with compromised wound healing ability (diabetics) and/or corneal inflammatory diseases (e.g. dry eye).
微小RNA调节众多生物学过程,使其成为潜在的治疗剂。这些分子的递送和稳定性问题限制了它们作为治疗手段的效用。我们证明,局部应用于完整眼表的合成高密度脂蛋白纳米颗粒(HDL NPs)可被上皮细胞和基质细胞摄取。与HDL NPs复合的微小RNA(miR-HDL NPs)同样被细胞和组织摄取并保留生物活性。与对照组相比,用HDL NPs或miR-HDL NPs局部治疗糖尿病小鼠,显著改善了伤口后的角膜再上皮化。用HDL NPs局部治疗的碱烧伤诱导炎症的小鼠角膜,在临床、形态学和免疫学方面均有改善。这些结果应为伤口愈合能力受损(糖尿病患者)和/或角膜炎症性疾病(如干眼症)患者带来一种基于HDL NPs的新型眼药水。