Fabrication of biocompatible magnetic maltose/MIL-88 metal–organic frameworks decorated with folic acid-chitosan for targeted and pH-responsive controlled release of doxorubicin

Abstract

Recently, metal–organic frameworks (MOFs) have attracted tremendous attention as promising porous drug delivery systems for cancer treatment. In this work, for the first time, a novel magnetic maltose disaccharide molecule modified with MIL-88 metal–organic framework (Fe3O4@C@MIL-88) was prepared, and then this targeted system was used for the delivery of the doxorubicin (DOX) drug. Eventually, Fe3O4@C@MIL-88-DOX were successfully decorated with folic acid conjugated chitosan (Fe3O4@C@MIL-88-DOX-FC) as a new targeted and controlled release drug system for treatment of MCF-7 breast cancer. The encapsulation efficiency of the DOX in the Fe3O4@C@MIL-88 was obtained at ∼83.6%. The in vitro drug release profiles showed a pH-responsive controlled release of DOX in acidic pH confirming the performance of the systems in the cancerous environment. The DOX release mechanism from systems at pH 5 also showed that the kinetic data well fitted to the Korsmeyer-Peppas and Fickian diffusion. Furthermore, in vitro cytotoxicity and DAPI staining study clearly illustrated that the synthesized Fe3O4@C@MIL-88 system had low cytotoxicity and good biocompatibility against MCF-7 cancer cells and MCF-10A normal cells. Whereas, Fe3O4@C@MIL-88-DOX and Fe3O4@C@MIL-88-DOX-FC exhibited good antitumor activity as a result of targeted delivery of DOX, which indicated the MCF-7 cell death with apoptotic effects. Based on these findings, the resulting carriers could be used as promising targeted drug delivery systems for cancer therapy.