Farace Cristiano, Sánchez-Moreno Paola, Orecchioni Marco, Manetti Roberto, Sgarrella Francesco, Asara Yolande, Peula-García José M, Marchal Juan A, Madeddu Roberto, Delogu Lucia G
Department of Biomedical Science, University of Sassari, 07100 Sassari, Italy.
Biocolloid and Fluid Physics Group, Department of Applied Physics, University of Granada, 18071 Granada, Spain.
Sci Rep. 2016 Jan 5;6:18423. doi: 10.1038/srep18423.
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.
脂质纳米胶囊（NCs）是临床诊断和治疗应用中很有前景的工具。然而，NC的适当功能化对于保证高生物相容性和分子负载能力至关重要。在任何医学应用中，不同功能化NCs对免疫系统的影响仍有待充分了解。本文报道了一项关于三种不同NC涂层（普朗尼克、壳聚糖和聚乙二醇-聚乳酸（PEG））对人外周血单核细胞（PBMCs）和主要免疫亚群作用的综合研究。在对颗粒进行深入表征后，通过流式细胞术和共聚焦显微镜评估摄取情况，然后重点关注对T细胞和单核细胞凋亡、坏死和增殖的影响。通过细胞直径变化、不同激活标志物分析和细胞因子检测来评估细胞功能。我们证明，NCs对免疫细胞反应的影响与其涂层密切相关。普朗尼克-NCs能够诱导先天免疫的免疫调节，从而诱导单核细胞激活。在用壳聚糖-NCs处理的单核细胞和T淋巴细胞中观察到了免疫调节。相反，PEG-NCs完全无活性。这些发现对于根据临床前研究的生物医学目的预先选择特定的NC涂层具有特别重要的价值；即特定NC涂层的免疫特异性作用对于免疫治疗应用可能非常出色。
