title: Calcium Carbonate Mineralized Nanoparticles as an Intracellular Transporter of Cytochrome c for Cancer Therapy.
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.
authors.affiliation: Department of Maxillofacial Biomedical Engineering &, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Ahn Na
authors.initials: AN
authors.lastname: Koo
authors.affiliation: Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Min
authors.affiliation: Department of Maxillofacial Biomedical Engineering &, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Hong Jae
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Maxillofacial Biomedical Engineering &, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Jegal
authors.affiliation: Department of Maxillofacial Biomedical Engineering &, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Maxillofacial Biomedical Engineering &, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, 130-701, Republic of Korea. schlee@khu.ac.kr.
authors.forename: Sang Cheon
authors.initials: SC
authors.lastname: Lee
mesh_terms: D017209:Apoptosis; D002119:Calcium Carbonate / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D000067493:Dynamic Light Scattering; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D010316:Particle Size; D011108:Polymers / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D011108:Polymers; D045304:Cytochromes c; D053148:Caspase 3; D002119:Calcium Carbonate
keywords: apoptosis; calcium; drug delivery; nanoparticles; proteins