Breast cancer is the primary cause of cancer-related death in women worldwide and its management remains a challenge in everyday oncology practice. Thus, development of new agents to treat breast cancer patients is very necessary. Curcumin (Cur), a natural product, exerts promising anti-cancer activities against various cancer types. However, its therapeutic efficacy is hindered due to poor aqueous solubility, rapid degradation, and low bioavailability. The objective of this study was to evaluate therapeutic potential of novel Cur-loaded multifunctional dendritic mesoporous silica nanoparticles (Cur-Ca@DMSNs-FA) for breast cancer treatment. Our results indicated that Cur-Ca@DMSNs-FA dispersed very well in aqueous solution, released Cur with a pH-responsible profile, and targeted efficiently into MCF-7 breast cancer cells. Further investigations revealed that Cur-Ca@DMSNs-FA can effectively inhibit cell proliferation, increase intracellular ROS generation, and decrease mitochondrial membrane potential along with a higher percentage of G2/M cell cycle arrest, thus leading to a greater apoptotic rates in MCF-7 compared with native Cur. Moreover, molecular basis of apoptosis studied by western blotting demonstrated that Cur-Ca@DMSNs-FA were more active than native Cur through suppression of PI3K/AKT/mTOR and Wnt/β-catenin signaling, also activation the mitochondria-mediated apoptosis pathway. In addition, hemolysis assay results showed that the Ca@DMSNs-FA exhibited good biocompatibility. Last, in vivo studies indicated that when Cur was encapsulated in Ca@DMSNs-FA, the Cur concentration in blood serum and tumor tissues was obvious increased after 1 h intraperitoneal injection. In conclusion, Cur-Ca@DMSNs-FA may be useful as a potential anticancer drug for treatment of breast cancer.

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