School of Pharmaceutical Sciences, University of Geneva, 1211 Geneva, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva, Switzerland.
Department of Radiology and Medical Informatics, University of Geneva, 1211 Geneva, Switzerland.
Eur J Pharm Biopharm. 2021 Jan;158:347-358. doi: 10.1016/j.ejpb.2020.11.017. Epub 2020 Nov 30.
Molecular medical imaging is intended to increase the accuracy of diagnosis, particularly in cardiovascular and cancer-related diseases, where early detection could significantly increase the treatment success rate. In this study, we present mixed micelles formed from four building blocks as a magnetic resonance imaging targeted contrast agent for the detection of atheroma and cancer cells. The building blocks are a gadolinium-loaded DOTA ring responsible for contrast enhancement, a fibrin-specific CREKA pentapeptide responsible for targeting, a fluorescent dye and DSPE-PEG. The micelles were fully characterized in terms of their size, zeta potential, stability, relaxivity and toxicity. Target binding assays performed on fibrin clots were quantified by fluorescence and image signal intensities and proved the binding power. An additional internalization assay showed that the micelles were also designed to specifically enter into cancer cells. Overall, these multimodal mixed micelles represent a potential formulation for MRI molecular imaging of atheroma and cancer cells.
分子医学成像旨在提高诊断的准确性,特别是在心血管和癌症相关疾病中,早期检测可以显著提高治疗成功率。在这项研究中,我们提出了由四个构建块组成的混合胶束作为磁共振成像靶向造影剂,用于检测动脉粥样硬化和癌细胞。构建块包括负责对比增强的载钆 DOTA 环、负责靶向的纤维蛋白特异性 CREKA 五肽、荧光染料和 DSPE-PEG。胶束的大小、zeta 电位、稳定性、弛豫率和毒性等方面进行了全面表征。在纤维蛋白凝块上进行的靶结合测定通过荧光和图像信号强度进行量化,并证明了结合能力。另外的内化测定表明,胶束也被设计为专门进入癌细胞。总的来说,这些多模式混合胶束代表了动脉粥样硬化和癌细胞的 MRI 分子成像的一种潜在制剂。