Nano Research

, Volume 8, Issue 5, pp 1546–1562 | Cite as

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. ZvyaginEmail author
Research Article


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.


nanoparticle upconversion surface modification biocompatibility cytotoxicity human skin 


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Copyright information

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Anna E. Guller
    • 1
    • 2
    • 4
  • Alla N. Generalova
    • 3
    • 4
  • Elena V. Petersen
    • 5
  • Andrey V. Nechaev
    • 4
    • 6
  • Inna A. Trusova
    • 5
  • Nikolay N. Landyshev
    • 5
  • Annemarie Nadort
    • 1
    • 7
  • Ekaterina A. Grebenik
    • 1
    • 3
    • 4
  • Sergey M. Deyev
    • 3
    • 4
  • Anatoly B. Shekhter
    • 2
  • Andrei V. Zvyagin
    • 1
    • 4
    Email author
  1. 1.Macquarie UniversitySydneyAustralia
  2. 2.I.M. Sechenov First Moscow State Medical UniversityMoscowRussia
  3. 3.Shemyakin-Ovchinnikov Institute of Bioorganic ChemistryRussian Academy of SciencesMoscowRussia
  4. 4.Nizhny Novgorod State UniversityNizhniy NovgorodRussia
  5. 5.Moscow Institute of Physics and TechnologyMoscowRussia
  6. 6.Moscow State University of Fine Chemical TechnologiesMoscowRussia
  7. 7.University of AmsterdamAmsterdamthe Netherlands

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