Morin-Loaded Nanoalloy-Reduced Graphene Oxide Nanoplatforms for Synergetic Chemotherapy to Target Metastatic Triple-Negative Breast Cancer

Abstract

Morin (Mrn), a bioflavonoid, is renowned for its numerous health benefits, particularly its potent anticancer and anticarcinogenic properties. Extensive research has been conducted on this compound as a therapeutic agent, but its low solubility and poor bioavailability limit its effectiveness in clinical settings. Graphene-based nanohybrids (GBNHs) have emerged as a promising strategy for efficiently administering Mrn in the treatment of triple-negative breast cancer (TNBC). This study presents a rapid and facile one-step synthesis of specially developed GBNHs. The purity of the NHs was confirmed using several characterization techniques. The loading efficiency of Mrn in the nanohybrids ranged from 85 to 95%, as quantified by high-performance liquid chromatography (HPLC). All nanohybrids exhibited excellent hemocompatibility with hemolysis rates below 2.63% and showed minimal cytotoxicity against normal fibroblast (3T3-L1) cells at concentrations up to 200 μg/mL. Among the tested nanohybrids, Mrn@Au/Ag-rGO demonstrated the highest cytotoxicity against MDA-MB-231 TNBC cells, with an IC₅₀ of 31.97 μg/mL, which is significantly lower than that of Mrn (61.73 μg/mL), Mrn@rGO (42.01 μg/mL), Mrn@Ag-rGO (46.85 μg/mL), and Mrn@Au-rGO (54.35 μg/mL). The anticancer activity of the NHs was attributed to metabolic reprogramming, G1 phase cell cycle arrest, inhibition of cell migration, modulation of reactive oxygen species (ROS) levels, and upregulation of apoptotic regulators such as p53, p-p53, and Bax at both gene and protein levels. These findings suggested that NHs may hold potential as a viable candidate for the treatment of TNBC.

Keywords: P53 tumor suppressor; TNBC; bimetallic nanoalloys; hemocompatibility; morin hydrate; nanohybrids.