title: pH-Responsive mineralized nanoparticles as stable nanocarriers for intracellular nitric oxide delivery.
abstract: We describe a calcium carbonate (CaCO3) mineralization approach to generate pH-responsive nanocarriers that can stably load S-nitrosoglutathione (GSNO) and dissolve at acidic endosomes to trigger intracellular release of nitric oxide (NO). GSNO-loaded CaCO3-mineralized nanoparticles (GSNO-MNPs) were prepared by an anionic block copolymer (PEG-Poly(l-aspartic acid))-templated mineralization. Ionic GSNO could be loaded in situ inside the CaCO3 core during the mineralization process. The stability of GSNO shielded within the crystalline CaCO3 core was greatly enhanced. The GSNO-MNPs triggered NO release at endosomal pH and an intracellular ascorbic acid level. Confocal microscopy demonstrated that the GSNO-MNPs could be dissolved at endosomal environments to release GSNO and sequentially generate NO through the GSNO reduction in the cytosol. In vitro cell experiments demonstrated that NO release by the GSNO-MNPs efficiently improved therapeutic activity of doxorubicin (DOX).
authors.affiliation: Department of Maxillofacial Biomedical Engineering and 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 Dentistry, Graduate School, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Da Eun
authors.initials: da E
authors.lastname: Kim
authors.affiliation: Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Park
authors.affiliation: Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Gi Hyun
authors.initials: GH
authors.lastname: Choi
authors.affiliation: Department of Dentistry, Graduate School, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Dal-Nim
authors.initials: DN
authors.lastname: Yang
authors.affiliation: Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: heojs@khu.ac.kr.
authors.forename: Jung Sun
authors.initials: JS
authors.lastname: Heo
authors.affiliation: Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: schlee@khu.ac.kr.
authors.forename: Sang Cheon
authors.initials: SC
authors.lastname: Lee
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology; D002119:Calcium Carbonate / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D003593:Cytoplasm / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry*; D026422:S-Nitrosoglutathione / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D011108:Polymers; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D004317:Doxorubicin; D002119:Calcium Carbonate
keywords: Calcium carbonate; Intracellular delivery; Mineralization; Nanocarrier; Nitric oxide