The Xaliproden Nanoscale Zirconium-Porphyrin Metal-Organic Framework (XAL-NPMOF) Promotes Photoreceptor Regeneration Following Oxidative and Inflammatory Insults.

IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY
International Journal of Nanomedicine Pub Date : 2024-10-15 eCollection Date: 2024-01-01 DOI:10.2147/IJN.S477011
Yajie Wang, Bo Yuan, Wei Liu, Jianlin Cui, Xueyan Zhou, Liyun Yuan, Zihao Deng, Yuhao Li, Xiaoyong Yuan
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引用次数: 0

Abstract

Background: Age-related macular degeneration (AMD) is becoming the leading cause of blindness in the aged population. The death of photoreceptors is the principal event which is lack of curative treatment. Xaliproden, a highly selective synthetic 5-OH-tryptamine (5HT) 1A receptor agonist, has the neuroprotective potential. However, its application has been limited by the insoluble formulation, low utilization efficiency and side effects caused by systemic administration.

Methods: Nanoscale zirconium-porphyrin metal-organic framework (NPMOF) was used as a skeleton and loaded with xaliproden (XAL) to prepare a novel kind of nanoparticle, namely, XAL-NPMOF. The human umbilical vein endothelial cells, zebrafish embryos and larvae were used to test the biotoxicity and fluorescence imaging capability of XAL-NPMOF both in vitro and in vivo. A photoreceptor degeneration model was generated by intense light injury in adult zebrafish and XAL-NPMOF was delivered to the injured retina by intraocular injection. The photoreceptor regeneration, inflammatory response and visual function were explored by immunohistochemistry, quantitative real-time polymerase chain reaction and optomotor response analysis.

Results: Following a single XAL-NPMOF intraocular injection, the injured retina underwent the faster photoreceptor regeneration with a recovery of visual function via promoting cell proliferation, suppressing the inflammatory responses and increasing the expression of antioxidases.

Conclusion: As an amplifier, NPMOF can enhance the anti-inflammatory efficacy and neuroprotective effect of xaliproden. XAL-NPMOF could be a novel and convenient option for the treatment of AMD.

Xaliproden纳米级锆卟啉金属有机框架(XAL-NPMOF)促进氧化和炎症损伤后的光感受器再生。
背景:老年性黄斑变性(AMD)正成为老年人失明的主要原因。光感受器的死亡是缺乏治疗方法的主要原因。Xaliproden是一种高选择性合成的5-OH-色胺(5HT)1A受体激动剂,具有保护神经的潜力。然而,由于其制剂不溶于水、利用效率低以及全身给药引起的副作用,其应用一直受到限制:方法:以纳米级锆卟啉金属有机框架(NPMOF)为骨架,负载Xaliproden(XAL),制备出一种新型纳米粒子,即XAL-NPMOF。利用人体脐静脉内皮细胞、斑马鱼胚胎和幼虫对 XAL-NPMOF 的生物毒性和荧光成像能力进行了体内外测试。通过强光损伤在成年斑马鱼体内建立光感受器变性模型,并通过眼内注射将 XAL-NPMOF 送入受伤的视网膜。通过免疫组化、实时定量聚合酶链式反应和视运动反应分析,研究了光感受器的再生、炎症反应和视觉功能:结果:单次眼内注射 XAL-NPMOF 后,通过促进细胞增殖、抑制炎症反应和增加抗氧化酶的表达,损伤视网膜的感光细胞再生速度加快,视功能恢复:结论:作为一种放大器,NPMOF能增强XAL-NPMOF的抗炎功效和神经保护作用。XAL-NPMOF可能是治疗老年性视网膜病变的一种新颖而便捷的选择。
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来源期刊
International Journal of Nanomedicine
International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY
CiteScore
14.40
自引率
3.80%
发文量
511
审稿时长
1.4 months
期刊介绍: The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.
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