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

SANDRA E MARTÍN; DIEGO CADENA CASTRO; PAULA M. UBERMAN; GERARDO GATTI; MÓNICA C. GARCÍA

NEW JOURNAL OF CHEMISTRY

ROYAL SOC CHEMISTRY

Lugar: CAMBRIDGE; Año: 2021 vol. 45 p. 4032 - 4045

1144-0546

Iron oxidenanoparticles are promising nanosystems for designing drug deliveryplatforms owning to their excellent biocompatibility and uniquemagnetic properties. Herein, we report for the first time a simpleand environmentally friendly methodology for obtaining stable hybridmagnetic nanoplatforms (HMNP) as nanocarriers for tamoxifen (TMX).Thus, Fe 3 O 4 nanoparticles were conjugated with L -cysteine ( L-Cys) and/or hyaluronic acid (HA). Two superparamagneticnanoplatforms, Fe 3 O 4 - L -Cys-HA and Fe 3 O 4 -HA (11 and 14 nm,respectively), were prepared. Their physicochemical andpharmaceutical properties, biocompatibility and cytotoxic effectagainst MCF-7 breast cancer cells were evaluated. The incorporationof L -Cys into the Fe 3 O 4 - L -Cys-HA HMNP effectively improvedtheir aqueous dispersibility and colloidal stability (up to 8 h).Both HMNP exhibited high TMX loading efficiency (460%), hydrophilicbehavior and magnetic response. TMX was released in a sustainedmanner and release kinetic data indicated diffusion-controlledrelease 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 oferythrocytes induced by the drug, and led to an unpredicted improveddrug efficacy. Four-fold lower concentration of HMNP-TMX (64 mM)improved TMX efficacy against MCF-7 breast cancer cells compared tothat of the free drug (256 mM). Thus, the HMNP-TMX increased drugcytotoxicity against tumor cells and reduced drug cytotoxicity in redblood cells, suggesting that they could offer a safety alternativefor controlled release of TMX with enhanced efficacy against breastcancer. Furthermore, the modular synthesis reported here opens up aninnovative method to rationalize the design and easy preparation ofHMNP for nanomedicinep { margin-bottom: 0.25cm; line-height: 115% }