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

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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.

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Authors and Affiliations

  1. Macquarie University, Sydney, Australia

    Anna E. Guller, Annemarie Nadort, Ekaterina A. Grebenik & Andrei V. Zvyagin

  2. I.M. Sechenov First Moscow State Medical University, Moscow, Russia

    Anna E. Guller & Anatoly B. Shekhter

  3. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia

    Alla N. Generalova, Ekaterina A. Grebenik & Sergey M. Deyev

  4. Nizhny Novgorod State University, Nizhniy Novgorod, Russia

    Anna E. Guller, Alla N. Generalova, Andrey V. Nechaev, Ekaterina A. Grebenik, Sergey M. Deyev & Andrei V. Zvyagin

  5. Moscow Institute of Physics and Technology, Moscow, Russia

    Elena V. Petersen, Inna A. Trusova & Nikolay N. Landyshev

  6. Moscow State University of Fine Chemical Technologies, Moscow, Russia

    Andrey V. Nechaev

  7. University of Amsterdam, Amsterdam, the Netherlands

    Annemarie Nadort

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  1. Anna E. Guller
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  2. Alla N. Generalova
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Guller, A.E., Generalova, A.N., Petersen, E.V. et al. Cytotoxicity and non-specific cellular uptake of bare and surface-modified upconversion nanoparticles in human skin cells. Nano Res. 8, 1546–1562 (2015). https://doi.org/10.1007/s12274-014-0641-6

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