• Cytotoxic Effects of Quercetin-Encapsulated PEG-PCL/Graphene Quantum Dot Nanoplatform on 5-FU-Resistant Gastric Cancer Cells
  • Parisa Javanali Azar,1,* Bahram Golestani Eimani,2 Kazem Nejati-Koshki,3
    1. MSc Student, Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Urmia Branch, Urmia, Iran
    3. Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil, Iran


  • Introduction: Gastric cancer is a primary global health concern and remains one of the leading causes of cancer-related deaths. Chemotherapy, particularly with 5-fluorouracil (5-FU), is a cornerstone of treatment. However, the effectiveness of 5-FU is often limited by the rapid development of drug resistance. Resistant tumor cells can survive despite drug exposure, leading to poor outcomes and treatment failure. To overcome this challenge, researchers are exploring new therapeutic strategies. Among these, nanocarrier-based delivery systems have shown promise by enhancing drug stability, improving cellular uptake, and enabling targeted delivery. Quercetin, a naturally occurring flavonoid, possesses anticancer properties but suffers from poor solubility and low bioavailability, limiting its clinical potential. This study investigated whether delivering Quercetin through PEG-PCL nanofibrous scaffolds functionalized with graphene quantum dots (GQDs) could enhance its cytotoxic effect on 5-FU–resistant gastric cancer cells.
  • Methods: PEG-PCL nanofibrous scaffolds were prepared using electrospinning and functionalized with graphene quantum dots to improve surface properties and drug-loading efficiency. Quercetin was incorporated into the scaffolds to generate the final nanocomposite system. Scanning electron microscopy (SEM) confirmed that the scaffolds exhibited uniform fiber morphology. The human gastric carcinoma MKN-45 cell line with acquired resistance to 5-FU was cultured under standard conditions and divided into four groups: (A) untreated control, (B) free Quercetin, (C) PEG-PCL/GQD scaffolds without drug, and (D) Quercetin-loaded PEG-PCL/GQD scaffolds. After 48 hours of treatment, cell viability was assessed using the MTT assay.
  • Results: Cells treated with Quercetin-loaded PEG-PCL/GQD scaffolds showed a marked reduction in viability compared with all other groups. Free Quercetin had a modest effect on cell survival, while the scaffolds without drug did not reduce viability, indicating the carrier system was biocompatible. The enhanced cytotoxic effect observed with the Quercetin-loaded nanoscaffolds demonstrates that this delivery system improves drug effectiveness in resistant cells, likely by facilitating uptake and sustained release. These findings suggest that combining Quercetin with PEG-PCL/GQD scaffolds can potentiate its anticancer activity in cells that are otherwise resistant to 5-FU.
  • Conclusion: PEG-PCL nanofibrous scaffolds functionalized with graphene quantum dots represent a promising delivery platform for Quercetin in the context of drug-resistant gastric cancer. By significantly decreasing the viability of 5-FU–resistant MKN-45 cells, this system offers a potential strategy to overcome chemoresistance. Further investigations are warranted to explore the molecular mechanisms underlying this effect and to assess the safety and efficacy of this approach in in vivo models. Overall, integrating natural anticancer compounds with advanced nanocarriers may provide a practical pathway toward improved therapies for gastric cancer.
  • Keywords: Gastric cancer, Chemoresistance, MKN-45, Quercetin, PEG-PCL