Real-Time Label-Free Monitoring of Nanoparticle Cell Uptake

Publication year: 2016
Authors: Suutari T. 1, Silen T. 1, S.en Karaman D. 2,3, Saari H. 1, Desai D. 2, Kerkelä E. 4, Laitinen S. 4, Hanzlikova M. 1, Rosenholm J.M. 2, Yliperttula M. 1,5, Viitala T. 6
Affiliations:

1 - Centre for Drug Research at the Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland
2 - Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, BioCity 3rd floor, Artillerigatan 6A, 20520, Åbo, Finland
3 - Centre for Functional Materials, Laboratory for Physical Chemistry, Faculty of Science and Engineering, Åbo Akademi University, Porthansgatan 3-5, 20500, Åbo, Finland
4 - Finnish Red Cross Blood Service, Kivihaantie 7, 00310, Helsinki, Finland
5 - Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via F. Marzolo 5, Padova, Italy.
6 - Centre for Drug Research at the Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland

Published in: Small
doi: 10.1002/smll.201601815

The surface plasmon resonance technique in combination with whole cell sensing is used for the first time for real-time label-free monitoring of nanoparticle cell uptake. The uptake kinetics of several types of nanoparticles relevant to drug delivery applications into HeLa cells is determined. The cell uptake of the nanoparticles is confirmed by confocal microscopy. The cell uptake of silica nanoparticles and polyethylenimine-plasmid DNA polyplexes is studied as a function of temperature, and the uptake energies are determined by Arrhenius plots. The phase transition temperature of the HeLa cell membrane is detected when monitoring cell uptake of silica nanoparticles at different temperatures. The HeLa cell uptake of the mesoporous silica nanoparticles is energy-independent at temperatures slightly higher than the phase transition temperature of the HeLa cell membrane, while the uptake of polyethylenimine-DNA polyplexes is energy-dependent and linear as a function of temperature with an activation energy of Ea = 62 ± 7 kJ mol-1 = 15 ± 2 kcal mol-1 . The HeLa cell uptake of red blood cell derived extracellular vesicles is also studied as a function of the extracellular vesicle concentration. The results show a concentration dependent behavior reaching a saturation level of the extracellular vesicle uptake by HeLa cells.


MP-SPR keywords: cell monolayer, cell uptake, changes in cells morphology, internalization of the cells, nanoparticle, polyethylenimine–plasmid DNA polyplexes, silica nanoparticles, soft materials, temperature dependent responses