Overcoming Resistance of Caco-2 Cells to 5-Fluorouracil through Diruthenium Complex Encapsulation in PMMA Nanoparticles.

Drug resistance, one of the main drawbacks in cancer chemotherapy, can be tackled by employing a combination of drugs that target different biological processes in the cell, enhancing the therapeutic efficacy. Herein, we report the synthesis and characterization of a new paddlewheel diruthenium complex that includes 5-fluorouracil (5-FU), a commonly used anticancer drug. This drug was functionalized with a carboxylate group to take advantage of the previously demonstrated release capacity of carboxylate ligands from the diruthenium core. The resulting hydrophobic complex, [Ru2Cl(DPhF)3(5-FUA)] (Ru-5-FUA) (DPhF = N,N'-diphenylformamidinate; 5-FUA = 5-fluorouracil-1-acetate) was subsequently entrapped in poly(methyl methacrylate) (PMMA) nanoparticles (PMMA@Ru-5-FUA) via a reprecipitation method to be transported in biological media. The optimized encapsulation procedure yielded particles with an average size of 81.2 nm, a PDI of 0.11, and a zeta potential of 29.2 mV. The cytotoxicity of the particles was tested in vitro using the human colon carcinoma cell line Caco-2. The IC50 (half maximal inhibitory concentration) of PMMA@Ru-5-FUA (6.08 µM) was just slightly lower than that found for the drug 5-FU (7.64 µM). Most importantly, while cells seemed to have developed drug resistance against 5-FU, PMMA@Ru-5-FUA showed an almost complete lethality at ∼30 µM. Conversely, an analogous diruthenium complex devoid of the 5-FU moiety, [Ru2Cl(DPhF)3(O2CCH3)] (PMMA@RuA), displayed a reduced cytotoxicity at equivalent concentrations. These findings highlight the effect of combining the anticancer properties of 5-FU with those of diruthenium species. This suggests that the distinct modes of action of the two chemical species are crucial for overcoming drug resistance.

Crystal structure of poly[[trans-di-aqua-bis-[µ2-trans-4,4'-(diazenedi-yl)dipyridine]-nickel(II)] diiodide ethanol disolvate].

In the title compound, {[Ni(C10H8N4)2(H2O)2]I2·2C2H5OH} n , the complex shows an octa-hedral environment of the Ni(2+) cation in which it is located on a centre of symmetry, linked to two water mol-ecules and the pyridine-N atoms of four 4,4'-(diazenediyl)dipyridine ligands bridging Ni(2+) cations along the b- and c-axis directions, giving rise to a two-dimensional arrangement. The Ni-N bond lengths are in the range 2.109 (4)-2.186 (3) Šand the Ni-O bond length is 2.080 (3) Å. The 4,4'-(diazenedi-yl)dipyridine ligand lies on an inversion centre. An O-H⋯O hydrogen-bond inter-action is observed between water and ethanol mol-ecules. The I(-) ions can be regarded as free anions in the crystal lattice.