Abstract

Drug delivery using nano-sized carriers holds tremendous potential for curing a range of diseases. The internalisation of nanoparticles by cells, however, remains poorly understood, restricting the possibility for optimising entrance into target cells, avoiding off-target cells and evading clearance. The majority of nanoparticle cell uptake studies have been performed in the presence of only the particle of interest; here, we instead report measurements of uptake when the cells are exposed to two different types of nanoparticles at the same time. We used carboxylated polystyrene nanoparticles of two different sizes as a model system and exposed them to HeLa cells in the presence of a biomolecular corona. Using flow cytometry, we quantify the uptake at both average and individual cell level. Consistent with previous literature, we show that uptake of the larger particles is impeded in the presence of competing smaller particles and, conversely, that uptake of the smaller particles is promoted by competing larger particles. While the mechanism(s) underlying these observations remain(s) undetermined, we are partly able to restrain the likely possibilities. In the future, these effects could conceivably be used to enhance uptake of nano-sized particles used for drug delivery, by administering two different types of particles at the same time.

Highlights

  • Using nano-sized carriers to deliver drugs holds great promise to cure a range of diseases [1,2,3,4], including cancers [5,6,7,8,9,10,11]

  • Nanoparticle internalisation by cells has been extensively studied, with particular attention paid to the internalisation pathways utilised by particles [12,13,14,15,16,17,18] and how they depend upon particle properties such as size [12,13,16,17,18,19,20], shape [12,13,16,17,18,20] and biomolecular corona [12,18]

  • These studies have been conducted in a range of different cell systems: simple adherent cells such as HeLa [21,22,23,24], U-2 OS [25] and A549 [26,27,28]; red blood cells [29,30]; barrier-forming cells such as Caco-2 [31], human umbilical vein endothelial cells [32] and bEnd3 [33]; three-dimensional cell systems [34,35]; and ex vivo tissue [36], to name a few

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Summary

Introduction

Using nano-sized carriers to deliver drugs holds great promise to cure a range of diseases [1,2,3,4], including cancers [5,6,7,8,9,10,11] In this endeavour, it is pertinent to understand how many carriers enter cells because the intracellular dose typically determines the therapeutic benefit [12,13,14].

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