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

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 mu g mL(-1), exhibited no cytotoxicity or inflammatory responses. By contrast, IONP-PMA showed a concentration-dependent increase of cytotoxicity and of TNF-alpha 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.