Department of Biology, Universidad Autónoma de Madrid (UAM), Darwin 2, Cantoblanco, 28049, Madrid, Spain.
Nanobiotechnology for Life Sciences Group, Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, Complutense University of Madrid (UCM), Plaza Ramón y Cajal, 28040, Madrid, Spain; Biomedical Research Networking Center for Respiratory Diseases (CIBERES), C/Melchor Fernandez-Almagro 3, 28029, Madrid, Spain; Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Melchor Fernandez Almagro, 3, 28029, Madrid, Spain.
Mater Sci Eng C Mater Biol Appl. 2020 Feb;107:110262. doi: 10.1016/j.msec.2019.110262. Epub 2019 Oct 11.
Magnetic resonance imaging (MRI) is the most powerful technique for non-invasive diagnosis of human diseases and disorders. Properly designed contrast agents can be accumulated in the damaged zone and be internalized by cells, becoming interesting cellular MRI probes for disease tracking and monitoring. However, this approach is sometimes limited by the relaxation rates of contrast agents currently in clinical use, which show neither optimal pharmacokinetic parameters nor toxicity. In this work, a suitable contrast agent candidate, based on iron oxide nanoparticles (IONPs) coated with polyethyleneglycol, was finely designed, prepared and fully characterized under a physical, chemical and biological point of view. To stand out the real potential of our study, all the experiments were performed in comparison with Ferumoxytol, a FDA approved IONPs. IONPs with a core size of 15 nm and coated with polyethyleneglycol of 5 kDa (OD15-P5) resulted the best ones, being able to be uptaken by both tumoral cells and macrophages and showing no toxicity for in vitro and in vivo experiments. In vitro and in vivo MRI results for OD15-P5 showed r relaxivity values higher than Ferumoxitol. Furthermore, the injected OD15-P5 were completely retained at the tumor site for up to 24 h showing high potential as MRI contrast agents for real time long-lasting monitoring of the tumor evolution.
磁共振成像(MRI)是诊断人类疾病和异常的最强大的非侵入性技术。适当设计的造影剂可以在损伤区域积累,并被细胞内化,成为用于疾病跟踪和监测的有趣的细胞 MRI 探针。然而,这种方法有时受到目前临床使用的造影剂弛豫率的限制,这些造影剂既没有最佳的药代动力学参数,也没有毒性。在这项工作中,基于氧化铁纳米粒子(IONP)的聚乙二醇(PEG)涂层的合适造影剂候选物,从物理、化学和生物学的角度进行了精细设计、制备和全面表征。为了突出我们研究的真正潜力,所有的实验都是与 FDA 批准的 IONP Ferumoxytol 进行比较。具有 15nm 核大小和 5kDa 聚乙二醇(OD15-P5)涂层的 IONP 是最好的,能够被肿瘤细胞和巨噬细胞摄取,并且在体外和体内实验中没有毒性。OD15-P5 的体外和体内 MRI 结果显示 r 弛豫率值高于 Ferumoxitol。此外,注射的 OD15-P5 在肿瘤部位最多可保留 24 小时,作为 MRI 造影剂具有很高的潜力,可实时长期监测肿瘤的演变。