Université de Strasbourg , CNRS, Institut de Physique et Chimie des Matériaux de Strasbourg, UMR 7504, F-67000 Strasbourg, France.
Fondation IcFRC/Université de Strasbourg , 8 allée Gaspard Monge BP 70028, F-67083 Strasbourg Cedex, France.
Mol Pharm. 2018 Feb 5;15(2):536-547. doi: 10.1021/acs.molpharmaceut.7b00904. Epub 2018 Jan 17.
The biodistribution of dendronized iron oxides, NPs10@D1_DOTAGA and melanin-targeting NPs10@D1_ICF_DOTAGA, was studied in vivo using magnetic resonance imaging (MRI) and planar scintigraphy through [Lu]Lu-radiolabeling. MRI experiments showed high contrast power of both dendronized nanoparticles (DPs) and hepatobiliary and urinary excretions. Little tumor uptake could be highlighted after intravenous injection probably as a consequence of the negatively charged DOTAGA-derivatized shell, which reduces the diffusion across the cells' membrane. Planar scintigraphy images demonstrated a moderate specific tumor uptake of melanoma-targeted [Lu]Lu-NPs10@D1_ICF_DOTAGA at 2 h post-intravenous injection (pi), and the highest tumor uptake of the control probe [Lu]Lu-NPs10@D1_DOTAGA at 30 min pi, probably due to the enhanced permeability and retention effect. In addition, ex vivo confocal microscopy studies showed a high specific targeting of human melanoma samples impregnated with NPs10@D1_ICF_Alexa647_ DOTAGA.
树状聚合物氧化铁 NPs10@D1_DOTAGA 和黑色素靶向 NPs10@D1_ICF_DOTAGA 的生物分布，通过 [Lu]Lu 放射性标记，使用磁共振成像（MRI）和平面闪烁显像术在体内进行了研究。MRI 实验表明，两种树状聚合物纳米粒子（DPs）都具有高的对比强度，并且具有肝胆和泌尿系统排泄。静脉注射后，肿瘤摄取量很少，可能是由于带负电荷的 DOTAGA 衍生壳减少了跨细胞膜的扩散。平面闪烁显像图像显示，静脉注射后 2 小时（pi），黑色素靶向 [Lu]Lu-NPs10@D1_ICF_DOTAGA 的肿瘤摄取具有中等特异性，而在 pi 时，对照组探针 [Lu]Lu-NPs10@D1_DOTAGA 的肿瘤摄取最高，可能是由于增强的通透性和保留效应。此外，离体共聚焦显微镜研究表明，用人黑色素瘤样本浸渍 NPs10@D1_ICF_Alexa647_DOTAGA 具有高度特异性靶向。
