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Mitochondrial Localization of Antioxidant Nanodrug Suppresses Ocular Inflammation by Alleviating Oxidative Stress on

Zhibin Ren1, Xiaoying Liu1, Guanghao Lv1

  • 1National Engineering Research Center of Ophthalmology and Optometry, School of Ophthalmology and Optometry & Biomedical Engineering, Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou, 325027, China.

Chemistry (Weinheim an Der Bergstrasse, Germany)
|January 20, 2025
PubMed

Insights

This study developed a novel nanodrug by conjugating caffeic acid with a peptide. The nanodrug effectively delivers antioxidants to cells, reducing oxidative stress and inflammation for potential ophthalmic disease treatment.

Area of Science:

  • Ocular Surface Science
  • Nanomedicine
  • Cellular Biology

Background:

  • External environmental factors induce oxidative stress on the ocular surface, leading to inflammation and apoptosis.
  • Antioxidants are a key strategy for managing oxidative stress in ophthalmic diseases.
  • Developing effective drug delivery systems is crucial for ocular therapeutics.

Purpose of the Study:

  • To create a peptide-drug conjugate nanodrug for targeted antioxidant delivery.
  • To investigate the cellular uptake, localization, and antioxidant efficacy of the nanodrug.
  • To evaluate the nanodrug's potential in mitigating inflammation and promoting cell survival.

Main Methods:

  • Conjugation of caffeic acid (polyphenolic antioxidant) with a peptide tag to form a self-assembling nanodrug.
  • Characterization of nanodrug uptake via caveolin-mediated endocytosis in human corneal epithelial cells (HCEC).
  • Assessment of antioxidant capacity through free radical scavenging and anti-inflammatory effects in lipopolysaccharide (LPS)-induced RAW 264.7 cells.

Main Results:

  • The nanodrug successfully localized caffeic acid within mitochondria after lysosomal escape.
  • Significant free radical scavenging activity was demonstrated by the nanodrug.
  • The nanodrug inhibited pro-inflammatory cytokines (NO, IL-6, TNF-α) and upregulated anti-apoptotic protein Bcl-2 in LPS-stimulated cells.

Conclusions:

  • Mitochondrial localization of antioxidants via this nanodrug effectively alleviates cellular oxidative stress.
  • The nanodrug demonstrates potential for regulating cellular redox balance and treating ocular diseases.
  • This approach offers novel insights for developing antioxidant drug delivery systems for clinical applications.
Keywords:
Anti-inflammationAnti-oxidationDrug deliveryMitochondrial localizationNanodrug

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