Issue 12, 2014

A general mechanism for intracellular toxicity of metal-containing nanoparticles


The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment – where particles are abundantly internalized – is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a “lysosome-enhanced Trojan horse effect” since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments.

Graphical abstract: A general mechanism for intracellular toxicity of metal-containing nanoparticles

Supplementary files

Article information

Article type
06 Mar 2014
06 Apr 2014
First published
09 Apr 2014
This article is Open Access
Creative Commons BY license

Nanoscale, 2014,6, 7052-7061

A general mechanism for intracellular toxicity of metal-containing nanoparticles

S. Sabella, R. P. Carney, V. Brunetti, M. A. Malvindi, N. Al-Juffali, G. Vecchio, S. M. Janes, O. M. Bakr, R. Cingolani, F. Stellacci and P. P. Pompa, Nanoscale, 2014, 6, 7052 DOI: 10.1039/C4NR01234H

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity