title: Encapsulation of selenium in chitosan nanoparticles improves selenium availability and protects cells from selenium-induced DNA damage response.
abstract: Selenium, an essential mineral, plays important roles in optimizing human health. Chitosan (CS) is an effective, naturally oriented material for synthesizing nanoparticles with preferable properties such as biocompatibility, biodegradation and resistance to certain enzymes. We have recently shown that cellular exposure to selenium compounds activates ataxia-telangiectasia mutated (ATM)-dependent DNA damage responses, a tumorigenesis barrier. To test whether nanoencapsulation of selenium modulates the cellular response to selenium compounds, the HCT 116 cancerous and the MRC-5 normal cells were treated with Na(2)SeO(3) and methylseleninic acid (MSeA) encapsulated in CS/polyphosphate nanoparticles. Analyses of cellular selenium levels demonstrate that (1) the nanoencapsulation enhances selenium levels in cells after exposure to Na(2)SeO(3) and MSeA (1-10 μM); (2) cells retained more selenium when treated with Na(2)SeO(3) than with MSeA; (3) selenium levels are greater in HCT 116 than in MRC-5 cells after Na(2)SeO(3), but not MSeA, exposure. Survival analysis shows that CS encapsulation desensitizes HCT 116 and MRC-5 cells to Na(2)SeO(3) or MSeA exposure. Immunofluorescent analysis demonstrates that CS encapsulation attenuates the selenium-induced ATM phosphorylation on Ser-1981, and the extent is greater in HCT 116 than in MRC-5 cells. Our results reveal features of selenium nanoencapsulation in CS, including increased selenium retention in cells and decreased cellular sensitivity and DNA damage response to selenium exposure.
authors.affiliation: Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.forename: Yangchao
authors.initials: Y
authors.lastname: Luo
authors.forename: Huawei
authors.initials: H
authors.lastname: Zeng
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Tian
authors.forename: Jiuzhou
authors.initials: J
authors.lastname: Song
authors.forename: Wen-Hsing
authors.initials: WH
authors.lastname: Cheng
mesh_terms: D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D045325:HCT116 Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D016566:Organoselenium Compounds / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012643:Selenium / Q000737:chemistry* / Q000493:pharmacokinetics*; D018038:Sodium Selenite / Q000737:chemistry / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016566:Organoselenium Compounds; D025521:Tumor Suppressor Proteins; D048271:Chitosan; C008493:methylselenic acid; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D012643:Selenium; D018038:Sodium Selenite