Hybrid magnetic nanoplatforms with L-cysteine and hyaluronic acid for controlled tamoxifen delivery in breast cancer therapy

CADENA, DIEGO; GATTI, GERARDO; MARTÍN, SANDRA; UBERMAN, PAULA; GARCÍA, MÓNICA C

CABA

Simposio; 1st Zooming into preclinical nanomedicines in the era Covid19; 2020

Nanomed-Ar

Fe-oxide nanoparticles (NP) are promising materials for designing drug delivery nanoplatforms owning their excellent biocompatibility and unique magnetic properties. A simple and environmentally friendly methodology for obtaining stable hybrid magnetic nanoplatforms (HMNP) as nanocarriers for tamoxifen (TMX) is reported. For that, Fe3O4 NP were conjugated with L-cysteine (L-Cys) and/or hyaluronic acid (HA). Two superparamagnetic nanoplatforms: Fe3O4-L-Cys-HA and Fe3O4-HA (11 and 14 nm, respectively) were prepared. Their physicochemical and pharmaceutical properties, hemocompatibility and cytotoxic effects against culture cells were evaluated. L-Cys effectively improved the aqueous dispersibility and colloidal stability (up to 8 h) of Fe3O4-L-Cys-HA. Both HMNP exhibited high TMX loading efficiencies (>60%), hydrophilic behavior and magnetic response. TMX was released in a sustained manner through diffusion-controlled release mechanisms. HMNP exhibited high hemocompatibility (hemolysis ≤5%) and low cytotoxicity against breast normal cells (MCF-10A); the load of TMX into HMNP reduced the hemolyzation of erythrocytes induced by the drug, and led to an unpredicted improved drug efficacy. Four-fold lower concentration of HMNP-TMX (64 µM) enhanced TMX efficacy against MCF-7 breast cancer cells compared to the free drug (256 µM). Thus, HMNP-TMX could offer a safety alternative for TMX controlled release with enhanced efficacy against breast cancer, demonstrating their potential in cancer nanomedicine.