Surface charge-specific cytotoxicity and cellular uptake of tri-block copolymer nanoparticles

S. Bhattacharjee, D.S. Ershov, J. van der Gucht, G.M. Alink, I. Rietjens, H. Zuilhof, A.T.M. Marcelis

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

A series of monodisperse (45 ± 5 nm) fluorescent nanoparticles from tri-block copolymers (polymeric nanoparticles (PNPs)) bearing different surface charges were synthesised and investigated for cytotoxicity in NR8383 and Caco-2 cells. The positive PNPs were more cytotoxic and induced a higher intracellular reactive oxygen species production than the neutral and negative ones. The cytotoxicity of positive PNPs with quaternary ammonium groups decreased with increasing steric bulk. The intracellular uptake and cellular interactions of these different PNPs were also tested in NR8383 cells by confocal laser scanning microscopy, which revealed higher uptake for positive than for negative PNPs. Also positive PNPs were found to interact much more with cell membranes, whereas the negative PNPs were internalised mainly by lysosomal endocytosis. Uptake of positive PNPs decreased with increasing steric bulk around the positive charge. A surface charge-specific interaction of clathrin for positive PNPs and caveolin receptors for negative PNPs was observed. These findings confirm that surface charge is important for the cytotoxicity of these PNPs, while they additionally point to considerable additional effects of the steric shielding around positive charges on PNP cytotoxicity.
Original languageEnglish
Pages (from-to)71-84
JournalNanotoxicology
Volume7
Issue number1
DOIs
Publication statusPublished - 2013

Fingerprint

Cytotoxicity
Surface charge
Nanoparticles
Block copolymers
Bearings (structural)
Caveolins
Clathrin
Caco-2 Cells
Cell membranes
Endocytosis
Ammonium Compounds
Confocal Microscopy
Shielding
Reactive Oxygen Species
Microscopic examination
Cell Membrane

Keywords

  • supported lipid-bilayers
  • cerium oxide nanoparticles
  • gold nanoparticles
  • oxidative stress
  • gene-expression
  • in-vitro
  • manufactured nanoparticles
  • chitosan nanoparticles
  • silicon nanoparticles
  • mitochondrial damage

Cite this

Bhattacharjee, S. ; Ershov, D.S. ; van der Gucht, J. ; Alink, G.M. ; Rietjens, I. ; Zuilhof, H. ; Marcelis, A.T.M. / Surface charge-specific cytotoxicity and cellular uptake of tri-block copolymer nanoparticles. In: Nanotoxicology. 2013 ; Vol. 7, No. 1. pp. 71-84.
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abstract = "A series of monodisperse (45 ± 5 nm) fluorescent nanoparticles from tri-block copolymers (polymeric nanoparticles (PNPs)) bearing different surface charges were synthesised and investigated for cytotoxicity in NR8383 and Caco-2 cells. The positive PNPs were more cytotoxic and induced a higher intracellular reactive oxygen species production than the neutral and negative ones. The cytotoxicity of positive PNPs with quaternary ammonium groups decreased with increasing steric bulk. The intracellular uptake and cellular interactions of these different PNPs were also tested in NR8383 cells by confocal laser scanning microscopy, which revealed higher uptake for positive than for negative PNPs. Also positive PNPs were found to interact much more with cell membranes, whereas the negative PNPs were internalised mainly by lysosomal endocytosis. Uptake of positive PNPs decreased with increasing steric bulk around the positive charge. A surface charge-specific interaction of clathrin for positive PNPs and caveolin receptors for negative PNPs was observed. These findings confirm that surface charge is important for the cytotoxicity of these PNPs, while they additionally point to considerable additional effects of the steric shielding around positive charges on PNP cytotoxicity.",
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Surface charge-specific cytotoxicity and cellular uptake of tri-block copolymer nanoparticles. / Bhattacharjee, S.; Ershov, D.S.; van der Gucht, J.; Alink, G.M.; Rietjens, I.; Zuilhof, H.; Marcelis, A.T.M.

In: Nanotoxicology, Vol. 7, No. 1, 2013, p. 71-84.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Surface charge-specific cytotoxicity and cellular uptake of tri-block copolymer nanoparticles

AU - Bhattacharjee, S.

AU - Ershov, D.S.

AU - van der Gucht, J.

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AU - Rietjens, I.

AU - Zuilhof, H.

AU - Marcelis, A.T.M.

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N2 - A series of monodisperse (45 ± 5 nm) fluorescent nanoparticles from tri-block copolymers (polymeric nanoparticles (PNPs)) bearing different surface charges were synthesised and investigated for cytotoxicity in NR8383 and Caco-2 cells. The positive PNPs were more cytotoxic and induced a higher intracellular reactive oxygen species production than the neutral and negative ones. The cytotoxicity of positive PNPs with quaternary ammonium groups decreased with increasing steric bulk. The intracellular uptake and cellular interactions of these different PNPs were also tested in NR8383 cells by confocal laser scanning microscopy, which revealed higher uptake for positive than for negative PNPs. Also positive PNPs were found to interact much more with cell membranes, whereas the negative PNPs were internalised mainly by lysosomal endocytosis. Uptake of positive PNPs decreased with increasing steric bulk around the positive charge. A surface charge-specific interaction of clathrin for positive PNPs and caveolin receptors for negative PNPs was observed. These findings confirm that surface charge is important for the cytotoxicity of these PNPs, while they additionally point to considerable additional effects of the steric shielding around positive charges on PNP cytotoxicity.

AB - A series of monodisperse (45 ± 5 nm) fluorescent nanoparticles from tri-block copolymers (polymeric nanoparticles (PNPs)) bearing different surface charges were synthesised and investigated for cytotoxicity in NR8383 and Caco-2 cells. The positive PNPs were more cytotoxic and induced a higher intracellular reactive oxygen species production than the neutral and negative ones. The cytotoxicity of positive PNPs with quaternary ammonium groups decreased with increasing steric bulk. The intracellular uptake and cellular interactions of these different PNPs were also tested in NR8383 cells by confocal laser scanning microscopy, which revealed higher uptake for positive than for negative PNPs. Also positive PNPs were found to interact much more with cell membranes, whereas the negative PNPs were internalised mainly by lysosomal endocytosis. Uptake of positive PNPs decreased with increasing steric bulk around the positive charge. A surface charge-specific interaction of clathrin for positive PNPs and caveolin receptors for negative PNPs was observed. These findings confirm that surface charge is important for the cytotoxicity of these PNPs, while they additionally point to considerable additional effects of the steric shielding around positive charges on PNP cytotoxicity.

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KW - gene-expression

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KW - manufactured nanoparticles

KW - chitosan nanoparticles

KW - silicon nanoparticles

KW - mitochondrial damage

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