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PEGylation of ORMOSIL nanoparticles differently modulates the in vitro toxicity toward human lung cells

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Abstract

ORganically MOdified SILica (ORMOSIL) nanoparticles (NPs) appear promising carriers for the delivery of drugs to target tissues but concerns on possible cytotoxic effects exist. Here, we studied the in vitro responses to ORMOSIL NPs in different types of human lung cells to determine the effects of polyethylene glycol (PEG) coating on NP cytotoxicity. Non-PEG NPs caused a concentration-dependent decrease of viability of all types of cells, while PEG NPs induced deleterious effects and death in carcinoma alveolar type II A549 cells but not in CCD-34Lu fibroblasts and NCI-H2347 adenocarcinoma cells. Reactive oxygen species were detected in cells incubated with PEG NPs, but their deactivation by superoxide dismutase and catalase did not protect A549 cells from death, suggesting that the oxidative stress was not the main determinant of cytotoxicity. Only in A549 cells PEG NPs modulated the transcription of genes involved in inflammation, signal transduction and cell death. Transmission electron microscopy evidenced a unique intracellular localization of PEG NPs in the lamellar bodies of A549 cells, which could be the most relevant factor leading to cytotoxicity by reducing the production of surfactant proteins and by interfering with the pulmonary surfactant system.

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Acknowledgments

The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 201031 NANOPHOTO and from Italian Ministry of Research (FIRB 2011, RBAP114AMK RINAME). We thank Dr. C. De Pittà (University of Padova) for the submission to GEO of the microarray data and Dr. E. Rampazzo (University of Bologna) for the generous gift of the rhodamine silane derivative. Microarray analysis was performed by CRIBI Gene Expression Service (MicroCribi, http://microcribi.cribi.unipd.it) of the University of Padova. The acquisition of the SEM and TEM images was performed by the electron microscopy service of the Department of Biology of University of Padova.

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The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Biology, University of Padova, Via U. Bassi 58/B, 35121, Padua, Italy

    Francesca Moret, Maddalena Mognato, Lucia Celotti & Elena Reddi

  2. Department of Chemical Sciences, University of Padova, Via F. Marzolo 1, 35131, Padua, Italy

    Francesco Selvestrel, Elisa Lubian & Fabrizio Mancin

  3. National Laboratory of Legnaro, INFN, Legnaro, Italy

    Lucia Celotti

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  1. Francesca Moret
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Correspondence to Elena Reddi.

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Moret, F., Selvestrel, F., Lubian, E. et al. PEGylation of ORMOSIL nanoparticles differently modulates the in vitro toxicity toward human lung cells. Arch Toxicol 89, 607–620 (2015). https://doi.org/10.1007/s00204-014-1273-z

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  • DOI: https://doi.org/10.1007/s00204-014-1273-z

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