Zeiringer Scarlett, Derler Martina, Mussbacher Marion, Kolesnik Tatjana, Fröhlich Eleonore, Leitinger Gerd, Kolb Dagmar, Tutz Sarah, Vargas Carolyn, Keller Sandro, Roblegg Eva
Institute of Pharmaceutical Sciences, Pharmaceutical Technology and Biopharmacy, University of Graz, Universitätsplatz 1, 8010 Graz, Austria.
Institute of Pharmaceutical Sciences, Pharmacology and Toxicology, University of Graz, Humboldtstraße 46/II, 8010 Graz, Austria.
Int J Mol Sci. 2025 May 28;26(11):5154. doi: 10.3390/ijms26115154.
The immunological barrier is among the most significant barriers in vivo. Macrophages and dendritic cells play a crucial role in immune responses, involving phagocytosis, antigen presentation, and triggering adaptive responses. Nanoscale drug-delivery vehicles, such as polymer-encapsulated lipid-bilayer nanodiscs, are of particular interest in the development of new therapeutic approaches, but require well-characterized human in vitro cell models. To this end, the present study differentiated human monocytes into two distinct states, resting macrophages and immature dendritic-like cells (iDCs). These cells served as model systems to assess the efficacy of lipid-bilayer nanodiscs encapsulated by anionic glyco-DIBMA (diisobutylene-maleic acid) or electroneutral sulfo-DIBMA polymers. Nanodisc-cell interaction studies-including cell viability, reactive oxygen species production, cytokine release, particle uptake, and activation marker expression-demonstrated that immune responses depend sensitively on the cell type and polymer and thus on the surface charge of the nanodiscs. Sulfo-DIBMA nanodiscs induced minimal immune cell activation, accompanied by cytokine release and reduced uptake of the nanodiscs by immune cells. In contrast, glyco-DIBMA nanodiscs exhibited increased interactions with cells, elicited pro-inflammatory immune responses, and promoted iDC maturation. This involved co-stimulatory and antigen-presenting molecules, potentially leading to T-cell activation. These findings underscore the potential of glyco-DIBMA nanodiscs to modulate immune responses through receptor-specific interactions, paving the way for immunotherapeutic strategies.
免疫屏障是体内最重要的屏障之一。巨噬细胞和树突状细胞在免疫反应中起关键作用，涉及吞噬作用、抗原呈递和触发适应性反应。纳米级药物递送载体，如聚合物包裹的脂质双层纳米盘，在新治疗方法的开发中特别受关注，但需要特征明确的人源体外细胞模型。为此，本研究将人单核细胞分化为两种不同状态，即静息巨噬细胞和未成熟树突状样细胞（iDCs）。这些细胞作为模型系统，用于评估由阴离子糖基 - DIBMA（二异丁烯 - 马来酸）或电中性磺基 - DIBMA聚合物包裹的脂质双层纳米盘的功效。纳米盘与细胞相互作用的研究——包括细胞活力、活性氧产生、细胞因子释放、颗粒摄取和激活标志物表达——表明免疫反应敏感地依赖于细胞类型和聚合物，进而依赖于纳米盘的表面电荷。磺基 - DIBMA纳米盘诱导的免疫细胞激活最小，同时伴有细胞因子释放和免疫细胞对纳米盘摄取的减少。相比之下，糖基 - DIBMA纳米盘与细胞的相互作用增加，引发促炎免疫反应，并促进iDC成熟。这涉及共刺激分子和抗原呈递分子，可能导致T细胞激活。这些发现强调了糖基 - DIBMA纳米盘通过受体特异性相互作用调节免疫反应的潜力，为免疫治疗策略铺平了道路。
