TPEN loaded poly (lactide-co-glycolide) nanoparticles promote neuroprotection and optic nerve regeneration

作者：Caiqing Wu, Haitao Zhang, Yuze Chen, Yangjiani Li, Yangjiani Li, Wei-Wei Jin, Jinpeng Yang, Yehong Zhuo, Ziyu Gao, Xiaohong Hu, Yiqing Li, Yiqing Li · 发表于：Materials Today Bio · 年份：2025 · DOI：10.1016/j.mtbio.2025.101670 · 被引用次数：7 · 研究领域：Neurological Disorders and Treatments、Alzheimer's disease research and treatments、Nerve injury and regeneration

Development of novel therapeutics for retinal ganglion cells (RGCs) protection and axon regeneration in neurodegenerative diseases, for example, glaucoma, are critical challenges in clinical treatment. Utilization of N, N, Nʹ, Nʹ-tetrakis-(2-Pyridylmethyl) ethylenediamine (TPEN), a specific chelator of Zn 2+ , revealed positive medical potentials. However, its therapeutic effect in promoting RGCs survival and axon regeneration is restricted due to the inefficient drug delivery and limited absorption. To address this, this work developed a novel nanoparticles (NPs)-based drug delivery system with sustained release of TPEN, using oil-in-water (O/W) single-emulsion solvent evaporation method with various surfaces coatings. Optic nerve crush (ONC) and acute ocular hypertension (AOH) animal models were carried out to investigate the neuroprotective and axon regenerative effects of TPEN-loaded NPs. RGCs protection was systematically assessed through whole-mount retina immunostaining and hematoxylin eosin staining for histological changes. Electroretinography was used for evaluating visual function changes. Axon protection and regeneration were evaluated by SMI32 stain and intravitreal administration of cholera Toxin Subunit B (CTB), respectively. In vivo , TPEN-loaded NPs achieved a comparable therapeutic effect on neuroprotection and axon regeneration after ONC, with a reduced frequency of vitreous injection and half of TPEN dosage compared to its solution. In the meantime, visual...