Abstract
Nanoparticles have been proposed as carriers for drugs, genes and therapies to treat various diseases1,2. Many strategies have been developed to target nanomaterials to specific or over-expressed receptors in diseased cells, and these typically involve functionalizing the surface of nanoparticles with proteins, antibodies or other biomolecules. Here, we show that the targeting ability of such functionalized nanoparticles may disappear when they are placed in a biological environment. Using transferrin-conjugated nanoparticles, we found that proteins in the media can shield transferrin from binding to both its targeted receptors on cells and soluble transferrin receptors. Although nanoparticles continue to enter cells, the targeting specificity of transferrin is lost. Our results suggest that when nanoparticles are placed in a complex biological environment, interaction with other proteins in the medium and the formation of a protein corona3,4 can ‘screen’ the targeting molecules on the surface of nanoparticles and cause loss of specificity in targeting.
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Acknowledgements
Funding for this project was 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), the Irish Research Council for Science, Engineering and Technology, the Helmholtz-Gemeinschaft Deutscher Forschungszentren e. V. Virtual Institute grant Nano Tracking (agreement no. VH-VI-421) and Science Foundation Ireland (09/RFP/MTR2425). This work was based on work supported by the Small Collaborative projects NeuroNano (NNP4-SL-2008-214547) and NanoTransKinetics (NMP4-2010-EU-US-266737), as well as the projects 3micron (NMP-2009-LARGE-3-246479) and NAMDIATREAM (NMP4-LA-2010-246479), funded by the European Commission 7th Framework Programme. The ESF Research Networking Programme EpitopeMap is also acknowledged, as well as use of the Conway Institute Flow Cytometry and Imaging Facilities and the Biological Imaging Suite at University College Dublin. J.C. Simpson is thanked for assistance with RNA interference experiments.
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A.S. performed experiments on cells, analysed and interpreted the data, and wrote the paper. A.S.P. performed biological interaction experiments, analysed and interpreted the data, and contributed to writing the paper. E.M. performed synthesis and characterization of nanoparticles, analysed and interpreted the data, and wrote the paper. M.P.M. prepared and characterized the depleted serum, analysed and interpreted the data, and contributed to writing the paper. K.P. contributed to silencing and competition experiments. D.R.H. and P.M.K. contributed to the synthesis and characterization of the particles, respectively. F.B.B. and C.Å. analysed and interpreted the data and contributed to writing the paper. K.A.D. conceived and designed the experiments, analysed and interpreted the data, and wrote the paper.
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Salvati, A., Pitek, A., Monopoli, M. et al. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nature Nanotech 8, 137–143 (2013). https://doi.org/10.1038/nnano.2012.237
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DOI: https://doi.org/10.1038/nnano.2012.237
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