A targeted biosystem based on l-lysine coated GO@rod-Cu(II) metal-organic frameworks for pH-controlled co-delivery of doxorubicin and curcumin

Abstract

Breast cancer is a leading cause of mortality in women worldwide and has attracted substantial research interest in the past several decades. Among the various cancer treatment methods, doxorubicin (DOX) and curcumin (CUR) are the most effective chemotherapeutic drugs to treat breast cancer. However, the remarkable side effects and systemic toxicity recorded by chemotherapeutic drugs mainly due to their lack of selectivity for cancer cells, short blood half-life, and nonspecific targeting, often lead to the failure of chemotherapy. Hence, the purpose of this work is to fabricate a new pH-controlled biosystem based on l-lysine amino acid coating on the surface of magnetic graphene oxide@rod-Cu(II) metal-organic frameworks (GO-Fe3O4@Cu MOFs-Lys) to overcome these challenges. The GO-Fe3O4@Cu MOFs and GO-Fe3O4@Cu MOFs-Lys encapsulation efficiency for DOX and CUR was 78.25%, 28.16%, 98.35%, and 45.78%, respectively. The in vitro simultaneous releasing of drugs revealed a controlled and pH-sensitive release behavior of GO-Fe3O4@Cu MOFs-Lys for DOX and CUR. Meanwhile, the drug release mechanism confirmed a Fickian diffusion-controlled release of drugs based on the Korsmeyer-Peppas model. The results of the in vitro cytotoxicity via MTT demonstrated the acceptable biocompatibility of the GO-Fe3O4@Cu MOFs-Lys against MCF-7 and MCF-10A cells and its MCF-7 cancer cell-killing capability after simultaneous loading of DOX and CUR. In addition, the in vitro hemolysis and antioxidant activity investigation revealed that the GO-Fe3O4@Cu MOFs-Lys had good haemocompatibility and excellent antioxidant activity. These results promoted us that the GO-Fe3O4@Cu MOFs-Lys as a new pH-sensitive biosystem could achieve a controlled release to oral drug delivery.