Organoselenium compounds as functionalizing agents for gold nanoparticles in cancer therapy

Gold nanoparticles (AuNPs) modified with four organoselenium compounds, i.e., 4-selenocyanatoaniline (com- pound 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 sys- tems 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.