Calcium Carbonate Mineralized Nanoparticles as an Intracellular Transporter of Cytochromec for Cancer Therapy

A new intracellular delivery system based on an apoptotic protein-loaded calcium carbonate (CaCO3) mineralized nanoparticle (MNP) is described. Apoptosis-inducing cytochromec (Cytc) loaded CaCO3 MNPs (Cytc MNPs) were prepared by block copolymer mediated in situ CaCO3 mineralization in the presence of Cytc. The resulting Cytc MNPs had a vaterite polymorph of CaCO3 with a mean hydrodynamic diameter of 360.5nm and exhibited 60% efficiency for Cytc loading. The Cytc MNPs were stable at physiological pH (pH7.4) and effectively prohibited the release of Cytc, whereas, at intracellular endosomal pH (pH5.0), Cytc release was facilitated. The MNPs enable the endosomal escape of Cytc for effective localization of Cytc in the cytosols of MCF-7 cells. Flow cytometry showed that the Cytc MNPs effectively induced apoptosis of MCF-7 cells. These findings indicate that the CaCO3 MNPs can meet the prerequisites for delivery of cell-impermeable therapeutic proteins for cancer therapy.