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<p>The development of effective strategies to counteract chemotherapy-induced cardiotoxicity is a growing priority in cancer therapeutics. Indirubin (INB), a bioactive compound with potent antioxidant properties, is hindered by its poor solubility and limited bioavailability. To address these limitations, INB-loaded nanoliposomes (NLP) were synthesized using the thin film hydration method. INB-NLP had a vesicular size of 82.5 ± 9.23&#xa0;nm, a zeta potential of − 27.4 mV, a PDI of 0.357, and an entrapment efficiency of 85 ± 9%, indicating favorable stability and pharmacokinetics. In vitro studies showed that INB-NLP effectively mitigates DNB toxicity, preserving cell morphology and viability, as confirmed by calcein AM assay and AO/EtBr staining. INB-NLP significantly reduced ROS generation, lipid peroxidation, iron accumulation and promoted cell cycle progression, confirmed by DCFH-DA, MDA, 4-HNE, Prussian blue staining, and cell cycle progression assessment. INB-NLP downregulated gene/protein expression of MMP9, IRP1/2, while upregulating ferritin mRNA and Gpx4, thereby preventing membrane degradation, restoring iron homeostasis, and enhancing antioxidant defence. Moreover, the upregulation of Top2β, decreased caspase 8, and modulation of cyt C suggest enhanced DNA repair, mitochondrial preservation, and reduced apoptosis. These findings underscore the potential of INB-NLP as a novel therapeutic approach for managing DNB cardiotoxicity.</p> Graphical Abstract <p></p>

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Pharmacological Intervention of Indirubin Loaded Nanoliposomes in Daunorubicin Mediated Cardiotoxicity: Ferroptosis Signalling Pathway Targeted Approach

  • 期刊论文

  • 发表日期：

    2025年12月17日

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  • Tani Carmel Raj T G,
  • Vennila Lakshmanan,
  • Nivedha Jayaseelan,
  • Kanimozhi Kaliyamoorthi,
  • Sindhu Ganapathy

摘要

The development of effective strategies to counteract chemotherapy-induced cardiotoxicity is a growing priority in cancer therapeutics. Indirubin (INB), a bioactive compound with potent antioxidant properties, is hindered by its poor solubility and limited bioavailability. To address these limitations, INB-loaded nanoliposomes (NLP) were synthesized using the thin film hydration method. INB-NLP had a vesicular size of 82.5 ± 9.23 nm, a zeta potential of − 27.4 mV, a PDI of 0.357, and an entrapment efficiency of 85 ± 9%, indicating favorable stability and pharmacokinetics. In vitro studies showed that INB-NLP effectively mitigates DNB toxicity, preserving cell morphology and viability, as confirmed by calcein AM assay and AO/EtBr staining. INB-NLP significantly reduced ROS generation, lipid peroxidation, iron accumulation and promoted cell cycle progression, confirmed by DCFH-DA, MDA, 4-HNE, Prussian blue staining, and cell cycle progression assessment. INB-NLP downregulated gene/protein expression of MMP9, IRP1/2, while upregulating ferritin mRNA and Gpx4, thereby preventing membrane degradation, restoring iron homeostasis, and enhancing antioxidant defence. Moreover, the upregulation of Top2β, decreased caspase 8, and modulation of cyt C suggest enhanced DNA repair, mitochondrial preservation, and reduced apoptosis. These findings underscore the potential of INB-NLP as a novel therapeutic approach for managing DNB cardiotoxicity.

Graphical Abstract