Luiz Cezar Barros Simonetti, Rodrigo de Almeida Romagna, Reginaldo Bezerra dos Santos, Edésia Martins Barros de Sousa, Anderson M. Peres, Emilly Stofel Ludovico, Rita de Cássia Ribeiro Gonçalves, Flávia Dayrell França, Letícia Neves Ferraz, Marcelo Antonio de Oliveira, Rodrigo Rezende Kitagawa, Gracielle Ferreira Andrade
Abstract Colorectal cancer is one of the most prevalent malignancies worldwide, with the global incidence projected to reach approximately 3.2 million cases by 2040. Mesoporous silica nanoparticles have been extensively investigated as promising drug delivery systems for cancer therapy. Chalcones, key precursors of flavonoids, have demonstrated notable cytotoxic activity, and structural modifications involving diverse functional groups have been shown to further enhance their antitumor efficacy. Within this context, we evaluated a synthetic chalcone against colorectal cancer cells (HCT-116) using the MTT tetrazolium assay. The 2′-hydroxy-2-fluorochalcone was incorporated into MCM-41 (Mobil Composition of Matter No. 41) and into matrices functionalized with 3-aminopropyltriethoxysilane (APTES) and folic acid. The nanoparticles were synthesized and characterized by thermogravimetric analysis (TGA), elemental analysis (CHN), scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta potential, and nitrogen adsorption. Evaluate its cytotoxicity in HCT-116 cells and selectivity (IS) with L-929 cells. Molecular docking showed interactions between amino acid residues and functional groups of 2′-hydroxy-2-fluorochalcone that was very important to its cytotoxicity and activity about proteins: thymidylate synthase and vascular endothelial growth factor receptor 2 (VEGFR2). In vitro release assay was carried out to verify the release profile of the chalcone from the nanoparticles. In vitro cytotoxic tests showed that the MCM-APTES-AF-CH sample improved the IC 50 [IC 50 of 2.73 ± 0.96 μM (IS: 5.66)] against the HCT-116 cells. Hemolysis assay showed that the samples did not cause hemolysis in the concentrations tested. These findings indicate that MCM-APTES-AF-CH represents a promising nanocarrier platform for enhancing the anticancer efficacy of novel chalcone derivatives against colorectal cancer cells.