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Abstract
A human blood cell model for immunotoxicity and genotoxicity testing was used to measure the response to polylactic-co-glycolic acid (PLGA-PEO) nanoparticle (NP) (0.12, 3, 15 and 75 μg/cm2 exposure in fresh peripheral whole blood cultures/isolated peripheral blood mononuclear cell cultures from human volunteers (n = 9–13). PLGA-PEO NPs were not toxic up to dose 3 μg/cm2; dose of 75 μg/cm2 displays significant decrease in [3H]-thymidine incorporation into DNA of proliferating cells after 4 h (70% of control) and 48 h (84%) exposure to NPs. In non-cytotoxic concentrations, in vitro assessment of the immunotoxic effects displayed moderate but significant suppression of proliferative activity of T-lymphocytes and T-dependent B-cell response in cultures stimulated with PWM > CON A, and no changes in PHA cultures. Decrease in proliferative function was the most significant in T-cells stimulated with CD3 antigen (up to 84%). Cytotoxicity of natural killer cells was suppressed moderately (92%) but significantly in middle-dosed cultures (4 h exposure). On the other hand, in low PLGA-PEO NPs dosed cultures, significant stimulation of phagocytic activity of granulocytes (119%) > monocytes (117%) and respiratory burst of phagocytes (122%) was recorded. Genotoxicity assessment revealed no increase in the number of micronucleated binucleated cells and no induction of SBs or oxidised DNA bases in PLGA-PEO-treated cells. To conclude on immuno- and genotoxicity of PLGA-PEO NPs, more experiments with various particle size, charge and composition need to be done.
Acknowledgements
We thank Helena Nagyova, Edita Mrvikova and Kristina Gavalova for technical help, to Advancell for providing PLGA-PEO NPs and their characteristics, as well as Antonio Marcomini and Davide Valotto (University Ca' Foscari of Venice, Italy), and Prof. Andrew Collins for his critical comments and all NanoTEST team. We acknowledge the support of the European Commission 7th Framework Programme for the NanoTEST project (Health-2007-1.3-4, Contract no: 201335), NANoREG (NMP.2012.1.3-3, Grant Agreement: 310584) and FP7 INFRA-2010-1.1.31, Contract no: 214547-2. This article was also supported by the ITMS project no.24240120033, Operational research and development program financed from the European Regional Development Fund.
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.