Polymeric Nanoparticles Limit the Collective Migration of Cellular Aggregates.

Grégory Beaune,Usharani Nagarajan,Françoise M Winnik,Françoise Brochard-Wyart

doi:10.1021/acs.langmuir.8b01736

Abstract

Controlling the propagation of primary tumors is fundamental to avoiding the epithelial to mesenchymal transition process leading to the dissemination and seeding of tumor cells throughout the body. Here we demonstrate that nanoparticles (NPs) limit the propagation of cell aggregates of CT26 murine carcinoma cells used as tumor models. The spreading behavior of these aggregates incubated with NPs is studied on fibronectin-coated substrates. The cells spread with the formation of a cell monolayer, the precursor film, around the aggregate. We study the effect of NPs added either during or after the formation of aggregates. We demonstrate that, in both cases, the spreading of the cell monolayer is slowed down in the presence of NPs and occurs only above a threshold concentration that depends on the size and surface chemistry of the NPs. The density of cells in the precursor films, measured by confocal microscopy, shows that the NPs stick cells together. The mechanism of slowdown is explained by the increase in cell–cell interactions due to the NPs adsorbed on the membrane of the cells. The present results demonstrate that NPs can modulate the collective migration of cells; therefore, they may have important implications for cancer treatment.

Highlights

Several recent in vivo studies, supported by in vitro mechanistic data, indicate that, inherently, gold nanoparticles (AuNP) are able to suppress or reduce the epithelial to mesenchymal transition (EMT) of tumor cells, a key process leading to cancer metastasis.[1]
Nanoparticles tested in these studies include citrated gold nanospheres (AuNPs), 5 to 20 nm in diameter,[2] used by Arvizo et al against epithelial ovarian cancer tumors, and 50-nm-long gold nanorods (AuNRs) coated with serum proteins shown by Zhou et al to reduce the metastatic ability of human breast cancer cells.[3]
The studies carried out in vivo and in vitro on isolated cells indicate that spherical AuNPs inhibit the proliferation of cancer cells by rescinding MAPK signaling and reverse EMT by up-regulating E-cadherin and reducing the secretion of proteins implicated in EMT.[2]

Summary

Introduction

Several recent in vivo studies, supported by in vitro mechanistic data, indicate that, inherently, gold nanoparticles (AuNP) are able to suppress or reduce the epithelial to mesenchymal transition (EMT) of tumor cells, a key process leading to cancer metastasis.[1]. Earlier work by Zhang et al indicated that the mobility of isolated primary human dermal fibroblasts was impaired by the addition of silica NPs (50 and 500 nm in size) via inhibition of the mRNA expression of adhesionrelevant genes.[7]

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