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rft.atitle Differential hERG ion channel activity of ultrasmall gold nanoparticles
rft.epage 8009
rft.genre article
rft.issn 0027-8424
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rft.jtitle Proceedings of the National Academy of Sciences of the United States of America
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rft.pub National Academy of Sciences
rft.date 2013-05-14
x.date 2013-05-14T00:00:00Z
rft.spage 8004
rft.volume 110
abstract <p>Understanding the mechanism of toxicity of nanomaterials remains a challenge with respect to both mechanisms involved and product regulation. Here we show toxicity of ultrasmall gold nanoparticles (AuNPs). Depending on the ligand chemistry, 1.4-nm-diameter AuNPs failed electrophysiology-based safety testing using human embryonic kidney cell line 293 cells expressing human ether-á-go-go-Related gene (hERG), a Food and Drug Administration-established drug safety test. In patch-clamp experiments, phosphine-stabilized AuNPs irreversibly blocked hERG channels, whereas thiol-stabilized AuNPs of similar size had no effect in vitro, and neither particle blocked the channel in vivo. We conclude that safety regulations may need to be reevaluated and adapted to reflect the fact that the binding modality of surface functional groups becomes a relevant parameter for the design of nanoscale bioactive compounds.</p>
authors Array ( [rft.aulast] => Leifert [rft.aufirst] => Annika )
Array ( [rft.aulast] => Pan [rft.aufirst] => Yu )
Array ( [rft.aulast] => Kinkeldey [rft.aufirst] => Anne )
Array ( [rft.aulast] => Schiefer [rft.aufirst] => Frank )
Array ( [rft.aulast] => Setzler [rft.aufirst] => Julia )
Array ( [rft.aulast] => Scheel [rft.aufirst] => Olaf )
Array ( [rft.aulast] => Lichtenbeld [rft.aufirst] => Hera )
Array ( [rft.aulast] => Schmid [rft.aufirst] => Günter )
Array ( [rft.aulast] => Wenzel [rft.aufirst] => Wolfgang )
Array ( [rft.aulast] => Jahnen-Dechent [rft.aufirst] => Willi )
Array ( [rft.aulast] => Simon [rft.aufirst] => Ulrich )
languages eng
url https://www.jstor.org/stable/42656626
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author Leifert, Annika, Pan, Yu, Kinkeldey, Anne, Schiefer, Frank, Setzler, Julia, Scheel, Olaf, Lichtenbeld, Hera, Schmid, Günter, Wenzel, Wolfgang, Jahnen-Dechent, Willi, Simon, Ulrich
author_facet Leifert, Annika, Pan, Yu, Kinkeldey, Anne, Schiefer, Frank, Setzler, Julia, Scheel, Olaf, Lichtenbeld, Hera, Schmid, Günter, Wenzel, Wolfgang, Jahnen-Dechent, Willi, Simon, Ulrich, Leifert, Annika, Pan, Yu, Kinkeldey, Anne, Schiefer, Frank, Setzler, Julia, Scheel, Olaf, Lichtenbeld, Hera, Schmid, Günter, Wenzel, Wolfgang, Jahnen-Dechent, Willi, Simon, Ulrich
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container_title Proceedings of the National Academy of Sciences of the United States of America
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description <p>Understanding the mechanism of toxicity of nanomaterials remains a challenge with respect to both mechanisms involved and product regulation. Here we show toxicity of ultrasmall gold nanoparticles (AuNPs). Depending on the ligand chemistry, 1.4-nm-diameter AuNPs failed electrophysiology-based safety testing using human embryonic kidney cell line 293 cells expressing human ether-á-go-go-Related gene (hERG), a Food and Drug Administration-established drug safety test. In patch-clamp experiments, phosphine-stabilized AuNPs irreversibly blocked hERG channels, whereas thiol-stabilized AuNPs of similar size had no effect in vitro, and neither particle blocked the channel in vivo. We conclude that safety regulations may need to be reevaluated and adapted to reflect the fact that the binding modality of surface functional groups becomes a relevant parameter for the design of nanoscale bioactive compounds.</p>
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mega_collection JSTOR Life Sciences Archive, JSTOR Health & General Sciences
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spelling Leifert, Annika Pan, Yu Kinkeldey, Anne Schiefer, Frank Setzler, Julia Scheel, Olaf Lichtenbeld, Hera Schmid, Günter Wenzel, Wolfgang Jahnen-Dechent, Willi Simon, Ulrich 0027-8424 National Academy of Sciences https://www.jstor.org/stable/42656626 <p>Understanding the mechanism of toxicity of nanomaterials remains a challenge with respect to both mechanisms involved and product regulation. Here we show toxicity of ultrasmall gold nanoparticles (AuNPs). Depending on the ligand chemistry, 1.4-nm-diameter AuNPs failed electrophysiology-based safety testing using human embryonic kidney cell line 293 cells expressing human ether-á-go-go-Related gene (hERG), a Food and Drug Administration-established drug safety test. In patch-clamp experiments, phosphine-stabilized AuNPs irreversibly blocked hERG channels, whereas thiol-stabilized AuNPs of similar size had no effect in vitro, and neither particle blocked the channel in vivo. We conclude that safety regulations may need to be reevaluated and adapted to reflect the fact that the binding modality of surface functional groups becomes a relevant parameter for the design of nanoscale bioactive compounds.</p> Differential hERG ion channel activity of ultrasmall gold nanoparticles Proceedings of the National Academy of Sciences of the United States of America
spellingShingle Leifert, Annika, Pan, Yu, Kinkeldey, Anne, Schiefer, Frank, Setzler, Julia, Scheel, Olaf, Lichtenbeld, Hera, Schmid, Günter, Wenzel, Wolfgang, Jahnen-Dechent, Willi, Simon, Ulrich, Proceedings of the National Academy of Sciences of the United States of America, Differential hERG ion channel activity of ultrasmall gold nanoparticles
title Differential hERG ion channel activity of ultrasmall gold nanoparticles
title_full Differential hERG ion channel activity of ultrasmall gold nanoparticles
title_fullStr Differential hERG ion channel activity of ultrasmall gold nanoparticles
title_full_unstemmed Differential hERG ion channel activity of ultrasmall gold nanoparticles
title_short Differential hERG ion channel activity of ultrasmall gold nanoparticles
title_sort differential herg ion channel activity of ultrasmall gold nanoparticles
title_unstemmed Differential hERG ion channel activity of ultrasmall gold nanoparticles
url https://www.jstor.org/stable/42656626