Intensificação do efeito antineoplásico de derivados de dibenzalacetonas por adsorção em nanopartículas de prata

Abstract

Cancer remains one of the major challenges in global public health, mainly due to the low selectivity of many conventional treatments and the occurrence of systemic adverse effects. In this context, dibenzalacetone derivatives (DDB) have attracted increasing interest because of their conjugated structure, chemical versatility, and potential antineoplastic activity. This study aimed to evaluate the adsorption of the derivatives DBD ((1E,4E)-1,5-bis[4- (dimethylamino)phenyl]penta-1,4-dien-3-one) and DBC ((1E,3E,6E,8E)-1,9-diphenylnona1,3,6,8-tetraen-5-one) onto silver nanoparticles modified with thiolated agents, as well as to investigate the spectroscopic properties and cytotoxic potential of the resulting hybrid systems. Silver nanoparticles (AgNPs) were synthesized by borohydride reduction and modified with 2- mercaptoethanol, 1-propanethiol, and 1,3-propanedithiol. The systems were characterized by ultraviolet-visible absorption spectroscopy (UV-VIS), Raman spectroscopy, infrared spectroscopy, dynamic light scattering, and theoretical calculations based on Density Functional Theory (DFT), with particular emphasis on Surface-Enhanced Raman Scattering spectroscopy (SERS). Cytotoxic activity was evaluated using the MTT assay (3-[4,5- dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) against the tumor cell lines A549, MDA-MB-231, and SK-MEL-28, as well as the healthy cell lines HaCaT and L929. The spectroscopic results indicated that surface modification of the nanoparticles favored the adsorption of the organic derivatives and the formation of electromagnetic field enhancement regions, enabling the acquisition of SERS spectra. Comparison between experimental and theoretical data demonstrated that DBD and DBC maintained their structural integrity after interacting with the metallic surface, with selective enhancement of vibrational modes associated with the π-conjugated system, aromatic rings, and the C=C–C=O axis. In the biological assays, the AgNPME+DBD system showed cytocompatibility in healthy cells and a greater effect against A549 and MDA-MB-231 cells. The AgNPME+DBC system, in turn, showed a more promising profile, reducing the viability of the three evaluated tumor cell lines while preserving, under most conditions, the viability of healthy cells above the cytocompatibility threshold. Therefore, the results suggest that the association between dibenzalacetone derivatives and modified silver nanoparticles represents a promising strategy for enhancing the antineoplastic effect, and SERS spectroscopy was essential for monitoring the adsorption of the active compounds.