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

Chem Asian J. 2015 Nov;10(11):2380-7. doi: 10.1002/asia.201500630. Epub 2015 Aug 26.

Abstract

A new intracellular delivery system based on an apoptotic protein-loaded calcium carbonate (CaCO3 ) mineralized nanoparticle (MNP) is described. Apoptosis-inducing cytochrome c (Cyt c) loaded CaCO3 MNPs (Cyt c MNPs) were prepared by block copolymer mediated in situ CaCO3 mineralization in the presence of Cyt c. The resulting Cyt c MNPs had a vaterite polymorph of CaCO3 with a mean hydrodynamic diameter of 360.5 nm and exhibited 60% efficiency for Cyt c loading. The Cyt c MNPs were stable at physiological pH (pH 7.4) and effectively prohibited the release of Cyt c, whereas, at intracellular endosomal pH (pH 5.0), Cyt c release was facilitated. The MNPs enable the endosomal escape of Cyt c for effective localization of Cyt c in the cytosols of MCF-7 cells. Flow cytometry showed that the Cyt c 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.

Keywords: apoptosis; calcium; drug delivery; nanoparticles; proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Calcium Carbonate / chemistry*
  • Caspase 3 / metabolism
  • Cytochromes c / administration & dosage
  • Cytochromes c / chemistry*
  • Cytochromes c / metabolism
  • Drug Carriers / chemistry
  • Dynamic Light Scattering
  • Humans
  • Hydrogen-Ion Concentration
  • MCF-7 Cells
  • Microscopy, Confocal
  • Nanoparticles / chemistry*
  • Neoplasms / drug therapy
  • Particle Size
  • Polymers / chemistry

Substances

  • Drug Carriers
  • Polymers
  • Cytochromes c
  • Caspase 3
  • Calcium Carbonate