Multichannel Ca 2+ Generator for Synergistic Tumor Therapy via Intracellular Ca 2+ Overload and Chemotherapy.

Ca 2+ overload has attracted an increasing attention due to its benefit of precise cancer therapy, but its efficacy is limited by the strong Ca 2+ excretion of cancer cells. Moreover, monotherapy of Ca 2+ overload usually fails to treat tumors satisfactorily. Herein, we develop a multifunctional nanosystem that could induce Ca 2+ 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 2+ generator to induce Ca 2+ overload directly in the intracellular environment by acid-triggered Ca 2+ release, while CUR could not only exhibit chemotherapy but also facilitate Ca 2+ release from the endoplasmic reticulum to the cytoplasm and inhibit Ca 2+ efflux out of cells to further enhance Ca 2+ 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 2+ overload and CUR-mediated chemotherapy. It is expected that the designed CaMSN@CUR has a great potential for effective tumor therapy.