Immune cell impact of three differently coated lipid nanocapsules: pluronic, chitosan and polyethylene glycol.

Lipid nanocapsules (NCs) represent promising tools in clinical practice for diagnosis and therapy applications. However, the NC appropriate functionalization is essential to guarantee high biocompatibility and molecule loading ability. In any medical application, the immune system-impact of differently functionalized NCs still remains to be fully understood. A comprehensive study on the action exerted on human peripheral blood mononuclear cells (PBMCs) and major immune subpopulations by three different NC coatings: pluronic, chitosan and polyethylene glycol-polylactic acid (PEG) is reported. After a deep particle characterization, the uptake was assessed by flow-cytometry and confocal microscopy, focusing then on apoptosis, necrosis and proliferation impact in T cells and monocytes. Cell functionality by cell diameter variations, different activation marker analysis and cytokine assays were performed. We demonstrated that the NCs impact on the immune cell response is strongly correlated to their coating. Pluronic-NCs were able to induce immunomodulation of innate immunity inducing monocyte activations. Immunomodulation was observed in monocytes and T lymphocytes treated with Chitosan-NCs. Conversely, PEG-NCs were completely inert. These findings are of particular value towards a pre-selection of specific NC coatings depending on biomedical purposes for pre-clinical investigations; i.e. the immune-specific action of particular NC coating can be excellent for immunotherapy applications.

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This work was partly supported by the Fondazione Banco di Sardegna (grant N° 2013.1308, 2014.6035 to L.G.D.), the University of Sassari (Italy), the Sardinia Region (grant N° CRP-59720 to L.G.D.), the Gianfranco del Prete Association “The future: medicine, biology and nanotechnology Award” to L.G.D, the Instituto de Salud Carlos III (FEDER funds, grant N° PI10/02295 to J.A.M), the Consejería de Economía, Innovación y Ciencia (Junta de Andalucía, excellence grant N° (CTS-6568 to J.A.M) and by the grant N° (MAT2013-43922-R).