Multichannel Ca Generator for Synergistic Tumor Therapy via Intracellular Ca Overload and Chemotherapy.

Ca overload has attracted an increasing attention due to its benefit of precise cancer therapy, but its efficacy is limited by the strong Ca excretion of cancer cells. Moreover, monotherapy of Ca overload usually fails to treat tumors satisfactorily. Herein, we develop a multifunctional nanosystem that could induce Ca overload by multipathway and simultaneously produce chemotherapy for synergistic tumor therapy. The nanosystem (CaMSN@CUR) is prepared by synthesizing a Ca-doped mesoporous silica nanoparticle (CaMSN) followed by loading the anticancer drug curcumin (CUR). CaMSN serves as the basis Ca generator to induce Ca overload directly in the intracellular environment by acid-triggered Ca release, while CUR could not only exhibit chemotherapy but also facilitate Ca release from the endoplasmic reticulum to the cytoplasm and inhibit Ca efflux out of cells to further enhance Ca overload. The in vitro and in vivo results show that CaMSN@CUR could exhibit a remarkable cytotoxicity against 4T1 cells and significantly inhibit tumor growth in 4T1 tumor-bearing mice via the synergy of Ca overload and CUR-mediated chemotherapy. It is expected that the designed CaMSN@CUR has a great potential for effective tumor therapy.