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Cerium(Iv) Oxide:Silver/Graphene Oxide (Ceo2:Ag/Go) Nanoparticles Modulate Gene Expression and Inhibit Colorectal Cancer Cell Growth: A Pathway-Centric Therapeutic Approach Publisher



Tamtaji OR1 ; Ostadian A2 ; Homayoonfal M3 ; Nejati M4 ; Mahjoubintehran M5, 6 ; Nabavizadeh F7 ; Ghelichi E8 ; Mohammadzadeh B9 ; Karimi M9 ; Rahimian N10, 11 ; Mirzaei H3
Authors
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Authors Affiliations
  1. 1. Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Laboratory Medicine, School of Allied Medical Sciences, Kashan University of Medical Sciences, Kashan, Iran
  3. 3. Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
  4. 4. Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
  5. 5. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
  6. 6. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
  7. 7. Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Department of Chemical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran
  9. 9. Institute of Nanoscience and Nanotechnology, University of Kashan, Kashan, Iran
  10. 10. Department of Internal Medicine, School of Medicine, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
  11. 11. Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences (IUMS), Tehran, Iran

Source: Cancer Nanotechnology Published:2024


Abstract

Colorectal cancer (CRC) represents a substantial global health burden, necessitating advancements in diagnostic and therapeutic modalities. This study aimed to investigate the potential of CeO2/GO nanoparticles (NPs) in managing CRC and to compare their efficacy with Ag-doped CeO2 (CeO2:Ag) NPs. The synthesis of cerium oxide (CeO2) and graphene oxide (GO) was meticulously performed, followed by a comprehensive evaluation of NPs' toxicity and their impact on apoptosis-related genes in CRC cells. Characterization techniques, including XRD, EDX, SEM, TEM, FT-IR, and DLS, validated the successful synthesis and unique properties of CeO2:Ag/GO NPs. XRD confirmed the CeO2 and GO structures, while EDX analysis confirmed high purity in the synthesized NPs and uniform element distribution in CeO2/GO NPs. SEM and TEM micrographs illustrated CeO2 NPs attached to graphene sheets, showcasing reduced size post-attachment. FT-IR revealed characteristic peaks for CeO2 and GO, confirming their composite structure. DLS showed an average NP size of 20 nm in solution. Notably, MTT assays demonstrated that CeO2:Ag/GO NPs exhibited enhanced cytotoxicity against CRC cells (C-26 cell line) compared to CeO2:Ag NPs, with higher doses showing heightened efficacy. CeO2:Ag/GO NPs induced stronger growth inhibition and apoptosis in CRC cells, which was linked to their improved cellular uptake and ability to target multiple cancer-related pathways. In contrast, GO NPs alone lacked cytotoxic effects. Gene expression analysis via qPCR revealed CeO2:Ag/GO NPs significantly downregulated Zeb-1, VEGF, Cyclin-D1, and Twist compared to controls, altering cancer-related pathways more effectively than CeO2:Ag NPs. Additionally, CeO2:Ag/GO NPs significantly upregulated BAX and Caspase-1 while downregulating Bcl-2, implicating a more potent apoptotic response. This study highlights the advantage of CeO2:Ag/GO NPs over CeO2:Ag NPs in impeding CRC cell growth and inducing apoptosis, offering a promising foundation for innovative therapeutic strategies. © The Author(s) 2024.
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