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<p>This study introduces an efficient protocol for loading chitosan nanocapsules with a nanocomposite comprising tea tree oil (TTO), ZnO, and Vitamin C (VC) to develop (TVCZ@CNC), a multi-targeted anticancer nanotherapeutic agent for renal cell carcinoma (RCC) cells (A498). TVCZ@CNC significantly reduced A498 cell viability to 40% (<i>P</i> &lt; .001) with an IC<sub>50</sub> of 15&#xa0;μg/ml, while maintaining 100% viability in Vero normal cells, demonstrating superior selective cytotoxicity compared to STP (20% A498 viability, 50% Vero viability). Cell cycle analysis revealed that TVCZ@CNC induced G0-G1 phase arrest (70% vs. 40% in the control, <i>P</i> &lt; .001) and decreased S-phase progression (20% vs. 30%, <i>p</i> &lt; .001). Gene expression profiling indicated that TVCZ@CNC downregulated CDK1, FGF2, VEGF, Fibronectin (<i>P</i> &lt; .05), and Bcl-2 (<i>P</i> &lt; .001), and upregulated TGFβ and Bax (<i>P</i> &lt; .001), suggesting the inhibition of proliferation, angiogenesis, and invasion. TVCZ@CNC triggered apoptosis in 18% of A498 cells and necrosis in 5%, comparable to STP (15% apoptosis, 3% necrosis, non-significant). Molecular docking analysis of TTO (terpinene-4-ol) and ZnO/VC for CDK1, VEGF, and fibronectin receptors revealed their inhibitory abilities. ZnO/VC showed significant bioactivity, with binding energies of −10.22&#xa0;kcal/mol for CDK1, −11.24, and − 8.09&#xa0;kcal/mol for fibronectin. TTO exhibited moderate bioactivity, forming fewer bonds than ZnO/VC, which formed seven bonds with VEGF. These interactions stabilize the complexes, thereby aiding in cancer cell inhibition. These findings highlight the potential of TVCZ@CNC as a selective, multi-mechanistic anticancer agent for RCC, warranting further in vivo studies to validate its therapeutic efficacy.</p>

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Synergistic Effects of Chitosan Nanocapsules with Tea Tree Oil, ZnO, and Vitamin C: Targeting Kidney Carcinoma through Multi-Pathway Proliferation Factors Inhibition and pro-Apoptotic Effects

  • 期刊论文

  • 发表日期：

    2025年11月12日

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  • Mohammad Y. Alfaifi,
  • Nasser E. M. Abosakr,
  • Mohammed El Behery,
  • Wesam Abd El-Fattah,
  • Serag Eldin I. Elbehairi,
  • Hani S. Hafez,
  • Reda F. M. Elshaarawy,
  • Lamia A. Ismail

摘要

This study introduces an efficient protocol for loading chitosan nanocapsules with a nanocomposite comprising tea tree oil (TTO), ZnO, and Vitamin C (VC) to develop (TVCZ@CNC), a multi-targeted anticancer nanotherapeutic agent for renal cell carcinoma (RCC) cells (A498). TVCZ@CNC significantly reduced A498 cell viability to 40% (P < .001) with an IC50 of 15 μg/ml, while maintaining 100% viability in Vero normal cells, demonstrating superior selective cytotoxicity compared to STP (20% A498 viability, 50% Vero viability). Cell cycle analysis revealed that TVCZ@CNC induced G0-G1 phase arrest (70% vs. 40% in the control, P < .001) and decreased S-phase progression (20% vs. 30%, p < .001). Gene expression profiling indicated that TVCZ@CNC downregulated CDK1, FGF2, VEGF, Fibronectin (P < .05), and Bcl-2 (P < .001), and upregulated TGFβ and Bax (P < .001), suggesting the inhibition of proliferation, angiogenesis, and invasion. TVCZ@CNC triggered apoptosis in 18% of A498 cells and necrosis in 5%, comparable to STP (15% apoptosis, 3% necrosis, non-significant). Molecular docking analysis of TTO (terpinene-4-ol) and ZnO/VC for CDK1, VEGF, and fibronectin receptors revealed their inhibitory abilities. ZnO/VC showed significant bioactivity, with binding energies of −10.22 kcal/mol for CDK1, −11.24, and − 8.09 kcal/mol for fibronectin. TTO exhibited moderate bioactivity, forming fewer bonds than ZnO/VC, which formed seven bonds with VEGF. These interactions stabilize the complexes, thereby aiding in cancer cell inhibition. These findings highlight the potential of TVCZ@CNC as a selective, multi-mechanistic anticancer agent for RCC, warranting further in vivo studies to validate its therapeutic efficacy.