Promising tamoxifen-loaded biocompatible hybrid magnetic nanoplatforms against breast cancer cells: synthesis, characterization and biological evaluation

Abstract

Iron oxide nanoparticles are promising nanosystems for designing drug delivery platforms owning to their excellent biocompatibility and unique magnetic properties. Herein, we report for the first time a simple and environmentally friendly methodology for obtaining stable hybrid magnetic nanoplatforms (HMNP) as nanocarriers for tamoxifen (TMX). Thus, Fe₃O₄ nanoparticles 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, biocompatibility and cytotoxic effect against MCF-7 breast cancer cells were evaluated. The incorporation of L-Cys into the Fe₃O₄-L-Cys-HA HMNP effectively improved their aqueous dispersibility and colloidal stability (up to 8 h). Both HMNP exhibited high TMX loading efficiency (>60%), hydrophilic behavior and magnetic response. TMX was released in a sustained manner and release kinetic data indicated diffusion-controlled release mechanisms. Both HMNP showed 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) improved TMX efficacy against MCF-7 breast cancer cells compared to that of the free drug (256 μM). Thus, the HMNP-TMX increased drug cytotoxicity against tumor cells and reduced drug cytotoxicity in red blood cells, suggesting that they could offer a safety alternative for controlled release of TMX with enhanced efficacy against breast cancer. Furthermore, the modular synthesis reported here opens up an innovative method to rationalize the design and easy preparation of HMNP for nanomedicine.