A pH-operated nanogate on mesoporous silica nanoparticles (MSNs) capable of simultaneous dual-cargo delivery of both metal ions and organic cargo molecules was used to deliver both Hoechst 33342 nuclear stain and calcium ions to MiaPaCa-2 cancer cells. Delivery of calcium to the cell cytoplasm to induce cellular death is an attractive alternative to using traditional, more hazardous chemotherapy drugs. Treatment of cancer cells with Hoechst-loaded, calcium-latched nanogate-modified MSNs resulted in the autonomous release of both cargo types, as visualized by cell nuclei staining and calcium-induced apoptosis. Apoptosis was confirmed by observation of nuclear fragmentation, chromatin condensation, and western blotting for cleaved caspase-3.