Targeted co-delivery of doxorubicin and methotrexate to breast cancer cells by a pH-sensitive biocompatible polymeric system based on β-cyclodextrin crosslinked glycodendrimer with magnetic ZnO core

Abstract

Nowadays, co-delivery of multiple therapeutics and combinational therapies using a delivery system is a promising approach to attain a synergistic anticancer effect. Hence, in the present study, we designed and synthesized a new pH-sensitive and biocompatible glycodendrimer immobilized on ZnO coated magnetic nanocomposite (Fe3O4@ZnO@CAMAD-β-CD) with antioxidant properties for co-delivery of doxorubicin (DOX) and methotrexate (MTX) to breast cancer cells. The structural properties of the new synthesized system were analyzed using various techniques. The drug loading results revealed that the Fe3O4@ZnO@CAMAD-β-CD nanocomposite displayed encapsulation efficiency (EE) of 96.08 % for DOX and 68.03 % for MTX. In vitro drug release study at pHs 5, 6.8, and 7.4 also showed that the release process was noticeably controlled, and pH-dependent manner with tumor target release behavior. Furthermore, the results of MTT cytotoxicity assessment, DAPI staining, confocal microscopy, and flow cytometry analysis against MDA-MB-231 breast cancer cell lines illustrated that the prepared Fe3O4@ZnO@CAMAD-β-CD has good biocompatibility and could easily enter the cells. The flow-cytometry analysis also showed that the apoptotic effects of DOX-MTX- Fe3O4@ZnO@CAMAD-β-CD have higher due to the synergistic effect in comparison to free drugs. The DPPH test for the study of antioxidant activity of Fe3O4@ZnO@CAMAD-β-CD nanocomposite showed that the carrier has excellent antioxidant activity (81.3 %). According to the results of this study, the prepared Fe3O4@ZnO@CAMAD-β-CD as a biocompatible carrier could be successfully used in the targeted co-delivery of DOX and MTX to cancer cells.