title: Intracellular trafficking pathways in silver nanoparticle uptake and toxicity in Caenorhabditis elegans.
abstract: We used the nematode Caenorhabditis elegans to study the roles of endocytosis and lysosomal function in uptake and subsequent toxicity of silver nanoparticles (AgNP) in vivo. To focus on AgNP uptake and effects rather than silver ion (AgNO3) effects, we used a minimally dissolvable AgNP, citrate-coated AgNPs (CIT-AgNPs). We found that the clathrin-mediated endocytosis inhibitor chlorpromazine reduced the toxicity of CIT-AgNPs but not AgNO3. We also tested the sensitivity of three endocytosis-deficient mutants (rme-1, rme-6 and rme-8) and two lysosomal function deficient mutants (cup-5 and glo-1) as compared to wild-type (N2 strain). One of the endocytosis-deficient mutants (rme-6) took up less silver and was resistant to the acute toxicity of CIT-AgNPs compared to N2s. None of those mutants showed altered sensitivity to AgNO3. Lysosome and lysosome-related organelle mutants were more sensitive to the growth-inhibiting effects of both CIT-AgNPs and AgNO3. Our study provides mechanistic evidence suggesting that early endosome formation is necessary for AgNP-induced toxicity in vivo, as rme-6 mutants were less sensitive to the toxic effects of AgNPs than C. elegans with mutations involved in later steps in the endocytic process.
authors.affiliation: a Nicholas School of the Environment, Duke University , Durham , NC , USA .|b Center for the Environmental Implications of Nanotechnology, Duke University , Durham , NC , USA .
authors.forename: Laura L
authors.initials: LL
authors.lastname: Maurer
authors.affiliation: a Nicholas School of the Environment, Duke University , Durham , NC , USA .|b Center for the Environmental Implications of Nanotechnology, Duke University , Durham , NC , USA .
authors.forename: Xinyu
authors.initials: X
authors.lastname: Yang
authors.affiliation: c Department of Biology , and.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Schindler
authors.affiliation: b Center for the Environmental Implications of Nanotechnology, Duke University , Durham , NC , USA .|d Department of Civil & Environmental Engineering , Duke University , Durham , NC , USA.
authors.forename: Ross K
authors.initials: RK
authors.lastname: Taggart
authors.affiliation: b Center for the Environmental Implications of Nanotechnology, Duke University , Durham , NC , USA .|d Department of Civil & Environmental Engineering , Duke University , Durham , NC , USA.
authors.forename: Chuanjia
authors.initials: C
authors.lastname: Jiang
authors.affiliation: b Center for the Environmental Implications of Nanotechnology, Duke University , Durham , NC , USA .|d Department of Civil & Environmental Engineering , Duke University , Durham , NC , USA.
authors.forename: Heileen
authors.initials: H
authors.lastname: Hsu-Kim
authors.affiliation: c Department of Biology , and.
authors.forename: David R
authors.initials: DR
authors.lastname: Sherwood
authors.affiliation: a Nicholas School of the Environment, Duke University , Durham , NC , USA .|b Center for the Environmental Implications of Nanotechnology, Duke University , Durham , NC , USA .
authors.forename: Joel N
authors.initials: JN
authors.lastname: Meyer
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D019343:Citric Acid / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins / Q000235:genetics; D004705:Endocytosis / Q000187:drug effects* / Q000235:genetics; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D009154:Mutation; D012834:Silver / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D012835:Silver Nitrate / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D023382:Toxicity Tests, Acute
chemical_list: D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; C486205:RME-1 protein, C elegans; C502292:RME-6 protein, C elegans; C489292:Rme-8 protein, Drosophila; D019343:Citric Acid; D012834:Silver; D012835:Silver Nitrate
keywords: In vivo endocytosis; lysosome; nanoparticle uptake; nanotoxicology