Lafuente-Gómez Nuria, Wang Shiqi, Fontana Flavia, Dhanjani Mónica, García-Soriano David, Correia Alexandra, Castellanos Milagros, Rodriguez Diaz Ciro, Salas Gorka, Santos Hélder A, Somoza Álvaro
Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), 28049, Madrid, Spain.
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Nanoscale. 2022 Aug 11;14(31):11129-11138. doi: 10.1039/d2nr01767a.
In this work, we describe the synthesis of magnetic nanoparticles composed of a maghemite core (MNP) and three different coatings (dextran, D-MNP; carboxymethyldextran, CMD-MNP; and dimercaptosuccinic acid, DMSA-MNP). Their interactions with red blood cells, plasma proteins, and macrophages were also assessed. CMD-MNP was selected for its good biosafety profile and for promoting a pro-inflammatory response in macrophages, which was associated with the nature of the coating. Thus, we proposed a smart miRNA delivery system using CMD-MNP as a carrier for cancer immunotherapy applications. Particularly, we prove that CMD-MNP-miRNA155 and CMD-MNP-miRNA125b nanoparticles can display a pro-inflammatory response in human macrophages by increasing the expression of CD80 and the levels of TNF-α and IL-6. Hence, our proposed miRNA-delivery nanosystem can be exploited as a new immunotherapeutic tool based on magnetic nanoparticles.
在这项工作中，我们描述了由磁赤铁矿核心（MNP）和三种不同涂层（葡聚糖，D-MNP；羧甲基葡聚糖，CMD-MNP；二巯基琥珀酸，DMSA-MNP）组成的磁性纳米颗粒的合成。还评估了它们与红细胞、血浆蛋白和巨噬细胞的相互作用。选择CMD-MNP是因为其良好的生物安全性以及能在巨噬细胞中促进促炎反应，这与涂层的性质有关。因此，我们提出了一种以CMD-MNP为载体的智能miRNA递送系统，用于癌症免疫治疗应用。特别地，我们证明了CMD-MNP-miRNA155和CMD-MNP-miRNA125b纳米颗粒可通过增加CD80的表达以及TNF-α和IL-6的水平，在人巨噬细胞中显示出促炎反应。因此，我们提出的miRNA递送纳米系统可作为一种基于磁性纳米颗粒的新型免疫治疗工具加以利用。
