Calcium carbonate end-capped, folate-mediated Fe3O4@mSiO2 core-shell nanocarriers as targeted controlled-release drug delivery system.

Magnetic mesoporous silica nanospheres (MMSN) were prepared and the surface was modified with cancer cell-specific ligand folic acid. Calcium carbonate was then employed as acid-activated gatekeepers to cap the mesopores of the MMSN, namely, MMSN-FA-CaCO3. The formation of the MMSN-FA-CaCO3 was proved by several characterization techniques, viz. transmission electron microscopy, zeta potential measurement, Fourier transform infrared spectroscopy, BET surface area measurement, and UV-Vis spectroscopy. Daunomycin was successfully loaded in the MMSN-FA-CaCO3 and the system exhibited sensitive pH stimuli-responsive release characteristics under blood or tumor microenvironment. Cellular uptake by folate receptor (FR)-overexpressing HeLa cells of the MMSN-FA-CaCO3 was higher than that by non-folated-conjugated ones. Intracellular-uptake studies revealed preferential uptake of these nanoparticles into FR-positive [FR(+)] HeLa than FR-negative [FR(-)]A549 cell lines. DAPI stain experiment showed high apoptotic rate of MMSN-FA-DNM-CaCO3 to HeLa cells. The present data suggest that the CaCO3 coating and folic acid modification of MMSN are able to create a targeted, pH-sensitive template for drug delivery system with application in cancer therapy.