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Cellular entry of nanoparticles via serum sensitive clathrin-mediated endocytosis, and plasma membrane permeabilization

Authors Smith, Giroud, Wiggins, Gower F, Thorley JA, Stolpe B, Mazzolin, Dyson, Rappoport J

Received 19 December 2011

Accepted for publication 22 February 2012

Published 24 April 2012 Volume 2012:7 Pages 2045—2055

DOI https://doi.org/10.2147/IJN.S29334

Review by Single-blind

Peer reviewer comments 3

Philip J Smith1, Maude Giroud2, Helen L Wiggins2, Florence Gower2, Jennifer A Thorley2, Bjorn Stolpe3, Julie Mazzolini2, Rosemary J Dyson4, Joshua Z Rappoport2
1Physical Sciences of Imaging for the Biomedical Sciences (PSIBS) Doctoral Training Center, School of Chemistry, 2School of Biosciences, 3School of Geography, Earth, and Environmental Sciences, 4School of Mathematics, University of Birmingham, Edgbaston, Birmingham, United Kingdom

Abstract: Increasing production and application of nanomaterials raises significant questions regarding the potential for cellular entry and toxicity of nanoparticles. It was observed that the presence of serum reduces the cellular association of 20 nm carboxylate-modified fluorescent polystyrene beads up to 20-fold, relative to cells incubated in serum-free media. Analysis by confocal microscopy demonstrated that the presence of serum greatly reduces the cell surface association of nanoparticles, as well as the potential for internalization. However, both in the presence and absence of serum, nanoparticle entry depends upon clathrin-mediated endocytosis. Finally, experiments performed with cells cooled to 4°C suggest that a proportion of the accumulation of nanoparticles in cells was likely due to direct permeabilization of the plasma membrane.

Keywords: nanoparticles, polystyrene beads, serum, endocytosis, dynamin, clathrin, permeabilization

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