<p>Breast cancer remains one of the leading causes of cancer-related mortality worldwide, highlighting the need for more effective and selective therapeutic strategies. In this study, a novel polycaprolactone–polyamidoamine (PCL–PAMAM) nanocarrier was developed for the co-delivery of silver nanoparticles (AgNPs) and sodium butyrate (NB) to MCF-7 breast cancer cells. The hybrid nanocarrier integrates the biocompatibility and biodegradability of PCL with the high functional group density of PAMAM dendrimers to enable efficient loading and controlled release of dual therapeutics.Physicochemical characterization confirmed successful synthesis, nanoscale size, uniform morphology, and high thermal stability of the fabricated system. The nanocarrier exhibited controlled and pH-responsive release of NB, with accelerated release under acidic conditions that mimic the tumor microenvironment. In vitro cytotoxicity studies demonstrated significantly enhanced antiproliferative activity of the co-loaded nanocarrier against MCF-7 cells compared to free sodium butyrate, while maintaining limited toxicity toward normal mesenchymal stem cells. Gene expression analysis revealed upregulation of pro-apoptotic markers (P53 and Caspase-9) and downregulation of the anti-apoptotic gene Bcl-2, indicating activation of the intrinsic apoptotic pathway. Overall, the results suggest that the PCL–PAMAM–Ag–NB nanocarrier represents a promising platform for synergistic and targeted breast cancer therapy through controlled drug delivery and apoptosis induction.</p>

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Developing efficient polymeric nanocarriers for dual therapeutics delivery to breast cancer cells in vitro studies

  • Sara Ismaile M-Abdualhussin,
  • Javad Mohammadnejad,
  • Asghar Narmani,
  • Hanieh Jafari,
  • Sevinj Jafarova Haqverdi,
  • Gülüzar Özbolat,
  • Yusuf Döğüş,
  • Guliyeva Ruhiyya Tahirağa,
  • Seyyedeh Touran Hosseini,
  • Amin Daemi

摘要

Breast cancer remains one of the leading causes of cancer-related mortality worldwide, highlighting the need for more effective and selective therapeutic strategies. In this study, a novel polycaprolactone–polyamidoamine (PCL–PAMAM) nanocarrier was developed for the co-delivery of silver nanoparticles (AgNPs) and sodium butyrate (NB) to MCF-7 breast cancer cells. The hybrid nanocarrier integrates the biocompatibility and biodegradability of PCL with the high functional group density of PAMAM dendrimers to enable efficient loading and controlled release of dual therapeutics.Physicochemical characterization confirmed successful synthesis, nanoscale size, uniform morphology, and high thermal stability of the fabricated system. The nanocarrier exhibited controlled and pH-responsive release of NB, with accelerated release under acidic conditions that mimic the tumor microenvironment. In vitro cytotoxicity studies demonstrated significantly enhanced antiproliferative activity of the co-loaded nanocarrier against MCF-7 cells compared to free sodium butyrate, while maintaining limited toxicity toward normal mesenchymal stem cells. Gene expression analysis revealed upregulation of pro-apoptotic markers (P53 and Caspase-9) and downregulation of the anti-apoptotic gene Bcl-2, indicating activation of the intrinsic apoptotic pathway. Overall, the results suggest that the PCL–PAMAM–Ag–NB nanocarrier represents a promising platform for synergistic and targeted breast cancer therapy through controlled drug delivery and apoptosis induction.