Actively targeted hyperbranched metal organic framework-based core–shell nanocarriers for the treatment of breast cancer

Abstract

Active-targeted nanocarriers are increasingly deployed for the precise and efficacious delivery of chemotherapeutic drugs to treat breast cancer (BC). This study portrays a BC-directed core–shell drug delivery system (DDS), where the core is made of a highly porous, biocompatible and drug accommodating metal organic framework, NH₂-MIL-101(Fe) MOF. Hence, the core is covalently linked with the hyperbranched dendrimer, G0.5-PAMAM. PAMAM confers multiple modifiable termini that are further functionalized with glutathione (GSH) as a targeting moiety. The prepared nanosystem (MPG) underwent physicochemical characterization using FTIR, ¹H-NMR, and PXRD, indicating the successful fabrication of the designed DDS. Additionally, TEM micrographs depicted an octahedral core with a size range of 100–150 nm. The assessed surface charge was +21 ± 0.2 indicating proper functionalization and colloidal stability of MPG. Besides, doxorubicin (DOX)-loaded MPG exhibited an entrapment efficiency of 65.3 ± 3% along with enhanced drug release in acidic medium. In addition, in vitro biological assays demonstrated that DOX-MPG possessed selective antiproliferative activity towards breast carcinoma cells (MCF-7) over normal cells (L929). Additionally, treatment with DOX-MPG efficiently induced apoptosis and G2/M cell cycle arrest in MCF7 cells. Finally, in vivo biological studies proved the therapeutic efficacy of DOX-MPG in mammary gland tumor-bearing mice. Conclusively, our findings suggest that the designed DDS offers a versatile platform for the delivery of active chemotherapeutic agents with superior selectivity and efficiency.