ENHANCED RADIOSENSITIZATION OF MELANOMA CELLS BY GOLD NANOPARTICLES AND POLYMERIC MICELLES COMBINED WITH DOXYCYCLINE

CAMMARATA A.; MARINO J.; DURÁN H.; GLISONI RJ.

Congreso; Reunión Anual de Sociedades de Biociencias SAIC SAFIS ALACF; 2024

Gold nanoparticles (AuNPs) were synthesized using polyoxyethylene (PEO) and polyoxypropylene (PPO) block copolymers (F127, F68, P85) through two methods: (i) direct formation in the presenceof reducing copolymers, creating AuNPs-PMs complexes, and (ii) preformed polymeric micelles (PMs) and AuNPs (by Turkevich synthesis) resulting in hybrid AuNPs/PMs blends. Doxycycline (Doxy), a mitochondrial biogenesis inhibitor which acts as an active ligand, was adsorbed onto the surface of these nanostructures. All nanosystems were characterized by UV-Visible, DLS and TEM. Hydrodynamic diameters (Dh) increased with higher copolymer molecular weights (MW) and concentrations (%w/v): AuNPs-PMs complexes ranged from 100-150 nm (0.5-5%) to 400-500 nm (10%); while AuNPs/PMs blends were slightly smaller, ranging from 20-60 nm (0.5-5%) to 500 nm (10%). P85 (lowest MW) displayed the smallest Dh (under 100 nm). All structures remained stable for 20 days. Copolymers prevented spontaneous AuNPs aggregation in presence of Doxy. Neither AuNPs (2.5-50μM), nor F127 and F68 PMs (0.1-1%) and their respective complexes and blends had a significantly impact on cell metabolic activity in A375 (radiosensitive) and Mel-J (radiresistant) melanoma cells. In contrast, free Doxy decreased melanoma cell viability below 75% at concentrations higher than 25μM, reaching 14-16% of viability at concentrations of ~1mM, whileDoxy (25μM) combined complexes and blends displayed a mayor reduction in cell viability (