PUBLICATION

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

Authors
Wang, Y., Yuan, B., Liu, W., Cui, J., Zhou, X., Yuan, L., Deng, Z., Li, Y., Yuan, X.
ID
ZDB-PUB-241022-5
Date
2024
Source
International Journal of Nanomedicine   19: 103871040010387-10400 (Journal)
Registered Authors
Cui, Jianlin, Li, Yuhao
Keywords
anti-inflammatory effect, nanoscale zirconium-porphyrin metal-organic framework, photoreceptor, regeneration, xaliproden
MeSH Terms
  • Regeneration*/drug effects
  • Zirconium*/chemistry
  • Zirconium*/pharmacology
  • Inflammation/drug therapy
  • Porphyrins*/chemistry
  • Porphyrins*/pharmacology
  • Zebrafish*
  • Metal-Organic Frameworks*/chemistry
  • Metal-Organic Frameworks*/pharmacology
  • Oxidative Stress/drug effects
  • Nanoparticles/chemistry
  • Humans
  • Photoreceptor Cells, Vertebrate/drug effects
  • Macular Degeneration/drug therapy
  • Human Umbilical Vein Endothelial Cells*/drug effects
  • Animals
PubMed
39430310 Full text @ Int. J. Nanomedicine
Abstract
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.
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.
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.
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.
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