A general mechanism for intracellular toxicity of metal-containing nanoparticles

Stefania Sabella, Randy Carney, Virgilio Brunetti, Maria Ada Malvindi, Noura Al-Juffali, Giuseppe Vecchio, Sam M. Janes, Osman M. Bakr, Roberto Cingolani, Francesco Stellacci, Pier Paolo Pompa

Research output: Contribution to journalArticlepeer-review

271 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)7052-7061
Number of pages10
Issue number12
StatePublished - Jun 21 2014
Externally publishedYes

ASJC Scopus subject areas

  • Materials Science(all)
  • Medicine(all)


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