Cytotoxicity and non-specific cellular uptake of bare and surface-modified upconversion nanoparticles in human skin cells

Anna E. Guller, Alla N. Generalova, Elena V. Petersen, Andrey V. Nechaev, Inna A. Trusova, Nikolay N. Landyshev, Annemarie Nadort, Ekaterina A. Grebenik, Sergey M. Deyev, Anatoly B. Shekhter, Andrei V. Zvyagin

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The cytotoxicity and non-specific cellular uptake of the most popular composition of upconversion nanoparticle (UCNP), NaYF4:Yb3+:Er3+, is reported using normal human skin cells, including dermal fibroblasts and immortalized human epidermal linear keratinocytes (HaCaT). A new hydrophilization reaction of as-synthesized UCNPs based on tetramethylammonium hydroxide (TMAH) enabled evaluation of the intrinsic cytotoxicity of bare UCNPs. The cytotoxicity effects of the UCNP surface-coating and polystyrene host were investigated over the concentration range 62.5–125 μg/mL with 24-h incubation, using a MTT test and optical microscopy. The fibroblast viability was not compromised by UCNPs, whereas the viability of keratinocytes varied from 52% ± 4% to 100% ± 10% than the control group, depending on the surface modification. Bare UCNPs reduced the keratinocyte viability to 76% ± 3%, while exhibiting profound non-specific cellular uptake. Hydrophilic poly(D,L-lactide)- and poly(maleic anhydride-alt-1-octadecene)-coated UCNPs were found to be least cytotoxic among the polymer-coated UCNPs, and were readily internalized by human skin cells. Polystyrene microbeads impregnated with UCNPs remained nontoxic. Surprisingly, no correlation was found between UCNP cytotoxicity and the internalization level in cells, although the latter ranged broadly from 0.03% to 59%, benchmarked against 100% uptake level of TMAH-UCNPs. [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)1546-1562
Number of pages17
JournalNano Research
Volume8
Issue number5
DOIs
Publication statusPublished - 18 May 2015
Externally publishedYes

Fingerprint

Cytotoxicity
Skin
Nanoparticles
Polystyrenes
Fibroblasts
Maleic Anhydrides
Maleic anhydride
Optical microscopy
Surface treatment
Polymers
Coatings
Chemical analysis
Keratinocytes
tetramethylammonium

Keywords

  • biocompatibility
  • cytotoxicity
  • human skin
  • nanoparticle
  • surface modification
  • upconversion

ASJC Scopus subject areas

  • Materials Science(all)
  • Electrical and Electronic Engineering

Cite this

Guller, A. E., Generalova, A. N., Petersen, E. V., Nechaev, A. V., Trusova, I. A., Landyshev, N. N., ... Zvyagin, A. V. (2015). Cytotoxicity and non-specific cellular uptake of bare and surface-modified upconversion nanoparticles in human skin cells. Nano Research, 8(5), 1546-1562. https://doi.org/10.1007/s12274-014-0641-6

Cytotoxicity and non-specific cellular uptake of bare and surface-modified upconversion nanoparticles in human skin cells. / Guller, Anna E.; Generalova, Alla N.; Petersen, Elena V.; Nechaev, Andrey V.; Trusova, Inna A.; Landyshev, Nikolay N.; Nadort, Annemarie; Grebenik, Ekaterina A.; Deyev, Sergey M.; Shekhter, Anatoly B.; Zvyagin, Andrei V.

In: Nano Research, Vol. 8, No. 5, 18.05.2015, p. 1546-1562.

Research output: Contribution to journalArticle

Guller, AE, Generalova, AN, Petersen, EV, Nechaev, AV, Trusova, IA, Landyshev, NN, Nadort, A, Grebenik, EA, Deyev, SM, Shekhter, AB & Zvyagin, AV 2015, 'Cytotoxicity and non-specific cellular uptake of bare and surface-modified upconversion nanoparticles in human skin cells', Nano Research, vol. 8, no. 5, pp. 1546-1562. https://doi.org/10.1007/s12274-014-0641-6
Guller, Anna E. ; Generalova, Alla N. ; Petersen, Elena V. ; Nechaev, Andrey V. ; Trusova, Inna A. ; Landyshev, Nikolay N. ; Nadort, Annemarie ; Grebenik, Ekaterina A. ; Deyev, Sergey M. ; Shekhter, Anatoly B. ; Zvyagin, Andrei V. / Cytotoxicity and non-specific cellular uptake of bare and surface-modified upconversion nanoparticles in human skin cells. In: Nano Research. 2015 ; Vol. 8, No. 5. pp. 1546-1562.
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abstract = "The cytotoxicity and non-specific cellular uptake of the most popular composition of upconversion nanoparticle (UCNP), NaYF4:Yb3+:Er3+, is reported using normal human skin cells, including dermal fibroblasts and immortalized human epidermal linear keratinocytes (HaCaT). A new hydrophilization reaction of as-synthesized UCNPs based on tetramethylammonium hydroxide (TMAH) enabled evaluation of the intrinsic cytotoxicity of bare UCNPs. The cytotoxicity effects of the UCNP surface-coating and polystyrene host were investigated over the concentration range 62.5–125 μg/mL with 24-h incubation, using a MTT test and optical microscopy. The fibroblast viability was not compromised by UCNPs, whereas the viability of keratinocytes varied from 52{\%} ± 4{\%} to 100{\%} ± 10{\%} than the control group, depending on the surface modification. Bare UCNPs reduced the keratinocyte viability to 76{\%} ± 3{\%}, while exhibiting profound non-specific cellular uptake. Hydrophilic poly(D,L-lactide)- and poly(maleic anhydride-alt-1-octadecene)-coated UCNPs were found to be least cytotoxic among the polymer-coated UCNPs, and were readily internalized by human skin cells. Polystyrene microbeads impregnated with UCNPs remained nontoxic. Surprisingly, no correlation was found between UCNP cytotoxicity and the internalization level in cells, although the latter ranged broadly from 0.03{\%} to 59{\%}, benchmarked against 100{\%} uptake level of TMAH-UCNPs. [Figure not available: see fulltext.]",
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