RT Journal Article
T1 Overcoming Resistance of Caco‑2 Cells to 5‑Fluorouracil through Diruthenium Complex Encapsulation in PMMA Nanoparticles
A1 Coloma Manjón-Cabeza, Isabel
A1 Parrón Ballesteros, Jorge
A1 Cortijo Montes, Miguel
A1 Cuerva de Alaiz, Cristian
A1 Turnay Abad, Francisco Javier
A1 Herrero Domínguez, Santiago
AB 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.
PB ACS Publications
YR 2024
FD 2024-06-04
LK https://hdl.handle.net/20.500.14352/105054
UL https://hdl.handle.net/20.500.14352/105054
LA eng
NO Overcoming Resistance of Caco-2 Cells to 5-Fluorouracil through Diruthenium Complex Encapsulation in PMMA Nanoparticles Isabel Coloma, Jorge Parrón-Ballesteros, Miguel Cortijo, Cristián Cuerva, Javier Turnay, and Santiago Herrero Inorganic Chemistry Article ASAP DOI: 10.1021/acs.inorgchem.4c01323
DS Docta Complutense
RD 24 jul 2024