Organoselenium compounds as functionalizing agents for gold nanoparticles in cancer therapy

Gold nanoparticles (AuNPs) modified with four organoselenium compounds, i.e., 4-selenocyanatoaniline (compound 1), 4,4'-diselanediyldianiline (compound 2), N-(4-selenocyanatophenyl)cinnamamide (compound 3), and N-(3-selenocyanatopropyl)cinnamamide (compound 4), were synthesized following two different approaches: direct conjugation and non-covalent immobilization onto hydrophilic and non-cytotoxic AuNPs functionalized with 3-mercapto-1-propanesulfonate (3MPS). Both free compounds and AuNPs-based systems were characterized via UV-Vis, FTIR NMR, mass spectrometry, and SR-XPS to assess their optical and structural properties. Size and colloidal stability were evaluated by DLS and ζ-potential measurements, whereas morphology at solid-state was evaluated by atomic force (AFM) and scanning electron (FESEM) microscopies. AuNPs synthesized through chemical reduction method in presence of Se-based compounds as functionalizing agents allowed the formation of aggregated NPs with little to no solubility in aqueous media. To improve their hydrophilicity and stability mixed AuNPs-3MPS-1 were synthesized. Besides, Se-loaded AuNPs-3MPS revealed to be the most suitable systems for biological studies in terms of size and colloidal stability. Selenium derivatives and AuNPs were tested in vitro via MTT assay against PC-3 (prostatic adenocarcinoma) and HCT-116 (colorectal carcinoma) cell lines. Compared to free compounds, direct functionalization onto AuNPs with formation of Au-Se covalent bond led to non-cytotoxic systems in the concentration range explored (0-100 μg/mL), whereas immobilization on AuNPs-3MPS improved the cytotoxicity of compounds 1, 3, and 4. Selective anticancer response against HCT-116 cells was obtained by AuNPs-3MPS-1. These results demonstrated that AuNPs can be used as a platform to tune the in vitro biological activity of organoselenium compounds.