Lerouge Frédéric, Ong Elodie, Rositi Hugo, Mpambani Francis, Berner Lise-Prune, Bolbos Radu, Olivier Cécile, Peyrin Françoise, Apputukan Vinu K, Monnereau Cyrille, Andraud Chantal, Chaput Frederic, Berthezène Yves, Braun Bettina, Jucker Mathias, Åslund Andreas Ko, Nyström Sofie, Hammarström Per, R Nilsson K Peter, Lindgren Mikael, Wiart Marlène, Chauveau Fabien, Parola Stephane
University of Lyon, École Normale Supérieure de Lyon, Laboratoire de Chimie, University of Lyon 1, CNRS UMR, 5182, Lyon, France.
University of Lyon, Lyon Neuroscience Research Center, CNRS UMR, 5292, INSERM U1028, University of Lyon 1, Lyon, France.
Nanomedicine (Lond). 2022 Dec;17(29):2173-2187. doi: 10.2217/nnm-2022-0252. Epub 2023 Mar 17.
To propose a new multimodal imaging agent targeting amyloid-β (Aβ) plaques in Alzheimer's disease. A new generation of hybrid contrast agents, based on gadolinium fluoride nanoparticles grafted with a pentameric luminescent-conjugated polythiophene, was designed, extensively characterized and evaluated in animal models of Alzheimer's disease through MRI, two-photon microscopy and synchrotron x-ray phase-contrast imaging. Two different grafting densities of luminescent-conjugated polythiophene were achieved while preserving colloidal stability and fluorescent properties, and without affecting biodistribution. brain uptake was dependent on the blood-brain barrier status. Nevertheless, multimodal imaging showed successful Aβ targeting in both transgenic mice and Aβ fibril-injected rats.
提出一种针对阿尔茨海默病中β淀粉样蛋白（Aβ）斑块的新型多模态成像剂。基于接枝有五聚体发光共轭聚噻吩的氟化钆纳米颗粒，设计了新一代混合造影剂，对其进行了广泛表征，并通过磁共振成像（MRI）、双光子显微镜和同步加速器X射线相衬成像在阿尔茨海默病动物模型中进行了评估。在保持胶体稳定性和荧光特性的同时，实现了两种不同接枝密度的发光共轭聚噻吩，且不影响生物分布。脑摄取取决于血脑屏障状态。尽管如此，多模态成像显示在转基因小鼠和注射Aβ原纤维的大鼠中均成功实现了Aβ靶向。
