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Iron oxide nanoparticles surface coating and cell uptake affect biocompatibility and inflammatory responses of endothelial cells and macrophages

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Abstract

Engineered iron oxide nanoparticles (IONP) offer the possibility of a wide range of medical uses, from clinical imaging to magnetically based hyperthermia for tumor treatment. These applications require their systemic administration in vivo. An important property of nanoparticles is their stability in biological media. For this purpose, a multicomponent nanoconstruct combining high colloidal stability and improved physical properties was synthesized and characterized. IONP were coated with an amphiphilic polymer (PMA), which confers colloidal stability, and were pegylated in order to obtain the nanoconstruct PEG-IONP-PMA. The aim of this study was to utilize cultured human endothelial cells (HUVEC) and murine macrophages, taken as model of cells exposed to NP after systemic administration, to assess the biocompatibility of PEG-IONP-PMA (23.1 ± 1.4 nm) or IONP-PMA (15.6 ± 3.4 nm). PEG-IONP-PMA, tested at different concentrations as high as 20 μg mL−1, exhibited no cytotoxicity or inflammatory responses. By contrast, IONP-PMA showed a concentration-dependent increase of cytotoxicity and of TNF-α production by macrophages and NO production by HUVECs. Cell uptake analysis suggested that after PEGylation, IONP were less internalized either by macrophages or by HUVEC. These results suggest that the choice of the polymer and the chemistry of surface functionalization are a crucial feature to confer to IONP biocompatibility.

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Acknowledgments

The authors report no conflict of interest. The authors are the sole responsible for the content and writing of the paper. This work was supported by grants from FAR 2010, FAR 2011, and “The MULAN Project” from Cariplo Foundation (Grant No. 2011-2096). We thank Pierre-Olivier Couraud for providing the hCMEC/D3 cells.

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Authors and Affiliations

  1. Department of Health Sciences, University of Milano-Bicocca, Via Cadore 48, 20900, Monza, Italy

    Antonina Orlando, Maria Gregori, Alice Panariti, Ilaria Rivolta, Massimo Masserini & Emanuela Cazzaniga

  2. Department of Biotechnology and Biosciences, University of Milano-Bicocca, piazza della Scienza 2, 20126, Milan, Italy

    Miriam Colombo & Davide Prosperi

  3. Nanomedicine Center NANOMIB, University of Milano-Bicocca, Milan, Italy

    Antonina Orlando, Miriam Colombo, Davide Prosperi, Maria Gregori, Ilaria Rivolta, Massimo Masserini & Emanuela Cazzaniga

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  1. Antonina Orlando
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Correspondence to Emanuela Cazzaniga.

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11051_2015_3148_MOESM1_ESM.eps

Supplementary material 1 (EPS 6039 kb) HUVECs and macrophages RAW264.7 viability after PEG-IONP treatment. HUVECs (A) and macrophages RAW264.7 (B) were incubated with different concentrations (20/50/100 µg mL–1) of PEG-IONP for 1 and 24 h and the mitochondrial activity was determined by MTT assay. The results are reported as percentage respect to control (untreated cells). Data are means ± S.E. of three separate experiments performed in triplicate. The results were compared by Student’s t-test. **=p<0.01; cnt=untreated cells. See text for abbreviations

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Orlando, A., Colombo, M., Prosperi, D. et al. Iron oxide nanoparticles surface coating and cell uptake affect biocompatibility and inflammatory responses of endothelial cells and macrophages. J Nanopart Res 17, 351 (2015). https://doi.org/10.1007/s11051-015-3148-5

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