Cerium(IV) oxide:silver/graphene oxide (CeO₂:Ag/GO) nanoparticles modulate gene expression and inhibit colorectal cancer cell growth: a pathway-centric therapeutic approach

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.