Díaz-Paredes Elena, Martín-Loro Francisco, Rodríguez-Marín Rocío, Gómez-Jaramillo Laura, Sánchez-Fernández Elena M, Carrillo-Carrión Carolina, Arroba Ana I
Department of Endocrinology, INiBICA, Puerta del Mar University Hospital, University of Cádiz, Avda. Ana de Viya 21, 11009 Cádiz, Spain.
Department of Organic Chemistry, Faculty of Chemistry, University of Sevilla, C/ Profesor García González 1, 41012 Sevilla, Spain.
Pharmaceutics. 2025 Jun 17;17(6):791. doi: 10.3390/pharmaceutics17060791.
Diabetic retinopathy is an ocular disease caused by changes in the expression of inflammatory mediators and increased oxidative stress in the retina and is the leading cause of vision loss in diabetic patients. Currently, there is no treatment capable of reversing retinal damage, which represents a significant burden on the quality of life of patients. (1)-1-Dodecylsulfonyl-5,6-oxomethylidenenojirimycin stands outs as a prototype of the sp-iminoglycolipids family for its beneficial neuroprotective effect against this chronic eye disease. Critical issues related to the low solubility and bioavailability of this glycolipid in biological settings are overcome by its encapsulation in a Zeolitic-Imidazolate Framework (ZIF) structure, resulting in homogeneous and biocompatible GlycoZIF nanoparticles. Cell studies show an enhanced cellular uptake compared with the free glycolipid, and importantly, its bioactivity is preserved once released inside cells. Extensive in vitro and ex vivo assays with diabetic retinopathy models unveil the mechanistic pathways of the designed GlycoZIF. A reduction in proinflammatory mediators, increased heme oxygenase-1 level, inhibition of NLRP3 inflammasome, and reduced reactive gliosis is shown. These findings demonstrate for the first time the potential of Glyco-modified ZIFs for the treatment of diabetes-related ocular problems by controlling the immune-mediated inflammatory response.
糖尿病视网膜病变是一种由视网膜中炎症介质表达变化和氧化应激增加引起的眼部疾病，是糖尿病患者视力丧失的主要原因。目前，尚无能够逆转视网膜损伤的治疗方法，这给患者的生活质量带来了巨大负担。(1)-1-十二烷基磺酰基-5,6-氧亚甲基野尻霉素作为sp-亚氨基糖脂家族的原型，因其对这种慢性眼病具有有益的神经保护作用而脱颖而出。通过将这种糖脂封装在沸石咪唑框架（ZIF）结构中，克服了其在生物环境中低溶解度和生物利用度的关键问题，从而得到了均匀且生物相容的糖基ZIF纳米颗粒。细胞研究表明，与游离糖脂相比，其细胞摄取有所增强，重要的是，一旦在细胞内释放，其生物活性得以保留。对糖尿病视网膜病变模型进行的广泛体外和离体试验揭示了所设计的糖基ZIF的作用机制途径。结果显示促炎介质减少、血红素加氧酶-1水平升高、NLRP3炎性小体受到抑制以及反应性胶质增生减少。这些发现首次证明了糖基修饰的ZIF通过控制免疫介导的炎症反应来治疗糖尿病相关眼部问题的潜力。
