Antifolate-modified iron oxide nanoparticles for targeted cancer therapy: inclusion vs. covalent union

Abstract

In this work four different iron oxide nanoparticles for the delivery of antitumoral drugs into cancer cells were synthesized and characterized. The antifolates raltitrexed, pemetrexed and methotrexate were bound to iron oxide nanoparticles by two different methods: covalent bonding or non-covalent interactions, such as electrostatic and H-bonding. For the covalent bonding of antifolates to the surface of nanoparticles an appropriate linker (3-aminopropyltriethoxysilane) was used, while the non-covalent interaction was achieved using nanoparticles functionalized in one step with squaramides and meso-2,3-dimercaptosuccinic acid. To evaluate the efficacy of the antifolate-derivatized nanoparticles, their cytotoxicity was assayed in A549 human lung adenocarcinoma cells. Only administration of the covalent antifolate-functionalized nanoparticles strongly inhibited the viability of these cancer cells, whereas the delivery of antifolates bound to nanoparticles through non-covalent interactions did not exhibit significant cytotoxic effects. The present results suggest that covalent antifolate-functionalized nanoparticles could be a potential delivery system for certain cancer cells.