Richard S, Boucher M, Saric A, Herbet A, Lalatonne Y, Petit P X, Mériaux S, Boquet D, Motte L
Laboratoire Matière et Systèmes Complexes (MSC), UMR 7057, CNRS and Université Paris Diderot, 75205 Paris Cedex 05, France.
J Mater Chem B. 2017 Apr 28;5(16):2896-2907. doi: 10.1039/c6tb03080g. Epub 2017 Apr 6.
PEGylation has been established as a valuable strategy to minimize nanoparticle clearance by the reticulo-endothelial system due to hydrophilicity and steric repulsion of PEG chains. In this study we functionalized superparamagnetic iron oxide nanoparticle surface with two PEG differing in their length (n = 23 and 44) and terminal functionality, COOH and CH. By varying the ratio of the two different PEG, we optimized the molecular architecture of the nanoplatform to obtain maximum stability and low toxicity under physiological conditions. The best nanoplatform was evaluated as MRI contrast for mouse brain vascularization imaging at 7 T. The carboxylic acid functions of the nanoplatform were used to covalently bind an antibody, Ab. This antibody, labeled with a fluorophore, targets the ET receptor, a G-protein-coupled receptor involved in the endothelin axis and overexpressed in various solid tumours, including ovarian, prostate, colon, breast, bladder and lung cancers. In vitro studies, performed by flow cytometry and magnetic quantification, showed the targeting efficiency of the Ab-nanoplatforms. Clearly, an imaging tracer for cancer diagnosis from a bimodal contrast agent (fluorescence and MRI) was thus obtained.
聚乙二醇化已成为一种有价值的策略，可通过聚乙二醇链的亲水性和空间排斥作用，将纳米颗粒被网状内皮系统清除的情况降至最低。在本研究中，我们用两种长度（n = 23和44）以及末端官能团（COOH和CH）不同的聚乙二醇对超顺磁性氧化铁纳米颗粒表面进行功能化处理。通过改变两种不同聚乙二醇的比例，我们优化了纳米平台的分子结构，以在生理条件下获得最大稳定性和低毒性。对最佳纳米平台进行了评估，将其作为7 T下小鼠脑血管成像的磁共振成像造影剂。纳米平台的羧酸官能团用于共价结合一种抗体Ab。这种用荧光团标记的抗体靶向内皮素受体，该受体是一种参与内皮素轴且在包括卵巢癌、前列腺癌、结肠癌、乳腺癌、膀胱癌和肺癌在内的各种实体瘤中过表达的G蛋白偶联受体。通过流式细胞术和磁性定量进行的体外研究显示了抗体 - 纳米平台的靶向效率。显然，由此获得了一种用于癌症诊断的双模态造影剂（荧光和磁共振成像）成像示踪剂。
