Abstract
Nanoparticles are considered a primary vehicle for targeted therapies because they can pass biological barriers and enter and distribute within cells by energy-dependent pathways1,2,3. So far, most studies have shown that nanoparticle properties, such as size4,5,6 and surface7,8, can influence how cells internalize nanoparticles. Here, we show that uptake of nanoparticles by cells is also influenced by their cell cycle phase. Although cells in different phases of the cell cycle were found to internalize nanoparticles at similar rates, after 24 h the concentration of nanoparticles in the cells could be ranked according to the different phases: G2/M > S > G0/G1. Nanoparticles that are internalized by cells are not exported from cells but are split between daughter cells when the parent cell divides. Our results suggest that future studies on nanoparticle uptake should consider the cell cycle, because, in a cell population, the dose of internalized nanoparticles in each cell varies as the cell advances through the cell cycle.
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Acknowledgements
Funding for the project was generously provided by the INSPIRE (Integrated NanoScience Platform for Ireland) programme, funded by the Irish Government's Programme for Research in Third Level Institutions, Cycle 4, National Development Plan 2007-2013 (J.A.K.), and the Irish Research Council for Science, Engineering and Technology (C.Å.), and is based on works supported by the Small Collaborative project NeuroNano funded by the European Commission 7th Framework Programme (NNP4-SL-2008-214547), Science Foundation Ireland (grant nos SFI/SRC/B1155 and 09/RFP/MTR2425) and the European Science Foundation Research Networking Programme EpitopeMap. A. Blanco (Conway Institute Flow Cytometry Facility, University College Dublin) is acknowledged for technical support with flow cytometry. Use of the Conway Institute Imaging Facility (University College Dublin) is also acknowledged. Endothelial hCMEC/D3 cells were provided by F. Miller and B.B. Wecksler (French National Institute of Health and Medical Research, Inserm, Paris, France).
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J.A.K. performed experiments, analysed and interpreted data, and wrote the paper. C.Å. developed the numerical simulations and analytical tools, analysed and interpreted data, and wrote the paper. A.S. supervised the experimental work, analysed and interpreted data, and wrote the paper. K.A.D. interpreted data and wrote the paper.
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Kim, J., Åberg, C., Salvati, A. et al. Role of cell cycle on the cellular uptake and dilution of nanoparticles in a cell population. Nature Nanotech 7, 62–68 (2012). https://doi.org/10.1038/nnano.2011.191
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DOI: https://doi.org/10.1038/nnano.2011.191
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