Cytotoxicity and non-specific cellular uptake of bare and surface-modified upconversion nanoparticles in human skin cells
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.
Keywordsnanoparticle upconversion surface modification biocompatibility cytotoxicity human skin
Unable to display preview. Download preview PDF.
- Wang, C.; Tao, H. Q.; Cheng, L.; Liu, Z. Near-infrared light induced in vivo photodynamic therapy of cancer based on upconversion nanoparticles. Biomaterials 2011, 32, 6145–6154.Google Scholar
- Atabaev, T. Sh.; Lee, J. H.; Han, D. W.; Hwang, Y. H.; Kim, H. K. Cytotoxicity and cell imaging potentials of submicron color-tunable yttria particles. J. Biomed. Mater. Res. Part A 2012, 100, 2287–2294.Google Scholar
- Gupta, B. K.; Narayanan, T. N.; Vithayathil, S. A.; Lee, Y.; Koshy, S.; Reddy, A. L. M.; Saha, A.; Shanker, V.; Singh, V. N.; Kaipparettu, B. A. et al. Highly luminescent-paramagnetic nanophosphor probes for in vitro high-contrast imaging of human breast cancer cells. Small 2012, 8, 3028–3034.CrossRefGoogle Scholar
- Mahajan, S.; Aalinkeel, R.; Reynolds, J.; Nair, B.; Sykes, D.; Law, W. C.; Prasad, P.; Schwartz, S. Innovative nanotherapy for the treatment of the chronic skin condition, rosacea (P3259). J. Immunol. 2013, 190, 192.Google Scholar
- Grebenik, E. A.; Nadort, A.; Generalova, A. N.; Nechaev, A. V.; Sreenivasan, V. K.; Khaydukov, E. V.; Semchishen, V. A.; Popov, A. P.; Sokolov, V. I.; Akhmanov, A. S. et al. Feasibility study of the optical imaging of a breast cancer lesion labeled with upconversion nanoparticle biocomplexes. J. Biomed. Opt. 2013, 18, 076004.CrossRefGoogle Scholar
- Andrade, Â. L.; Fabris, J. D.; Ardisson, J. D.; Valente, M. A.; Ferreira, J. M. F. Effect of tetramethylammonium hydroxide on nucleation, surface modification and growth of magnetic nanoparticles. J. Nanomater. 2012, 2012, 1–10.Google Scholar
- Generalova, A. N.; Kochneva, I. K.; Khaydukov, E. V.; Semchishen, V. A.; Guller, A. E.; Nechaev, A. V.; Shekhter, A. B.; Zubov, V. P.; Zvyagin, A. V.; Deyev, S. M. Submicron polyacrolein particles in situ embedded with upconversion nanoparticles for bioassay. Nanoscale 2014, DOI: 10.1039/c4nr05908e.Google Scholar
- Takashima A. Establishment of fibroblast cultures. Curr. Protoc. Cell Biol. 2001, Chapter 2: Unit 2.1. DOI: 10.1002/0471143030.cb0201s00.Google Scholar
- Sheftel, V. O.; Kataeva, S. E. Migration of Harmful Chemicals from Polymeric Materials. Khimiya: Moscow, 1978.Google Scholar