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The origin of heterogeneous nanoparticle uptake by cells

Published version
Peer-reviewed

Type

Article

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Authors

Rees, Paul 
Barnes, Claire 
Brown, Rowan 
Summers, Huw 

Abstract

Understanding nanoparticle uptake by biological cells is fundamentally important to wide-ranging fields from nanotoxicology to drug delivery. It is now accepted that the arrival of nanoparticles at the cell is an extremely complicated process, shaped by many factors including unique nanoparticle physico-chemical characteristics, protein-particle interactions and subsequent agglomeration, diffusion and sedimentation. Sequentially, the nanoparticle internalisation process itself is also complex, and controlled by multiple aspects of a cell’s state. Despite this multitude of factors, here we demonstrate that the statistical distribution of the nanoparticle dose per endosome is independent of the initial administered dose and exposure duration. Rather, it is the number of nanoparticle containing endosomes that are dependent on these initial dosing conditions. These observations explain the heterogeneity of nanoparticle delivery at the cellular level and allow the derivation of simple, yet powerful probabilistic distributions that accurately predict the nanoparticle dose delivered to individual cells across a population.

Description

Keywords

A549 Cells, Biological Transport, Cell Line, Endosomes, High-Throughput Screening Assays, Humans, Image Processing, Computer-Assisted, Microscopy, Confocal, Nanoparticles

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

10

Publisher

Nature Publishing Group

Rights

All rights reserved
Sponsorship
J.W.W. would like to acknowledge Girton College and the Herchel Smith Fund of Cambridge for providing him with a post-doctoral Fellowship. The authors are grateful to J.J. Powell and S. H. Doak for their critical insights. This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) (grant number EP/H008683/1). P.R. and H.D.S. would also like to acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC) under grants BB/N005163/1 and BB/P026818/1.