Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China.
Molecules. 2019 Apr 15;24(8):1477. doi: 10.3390/molecules24081477.
We developed a tumor-targeted contrast agent based on linear polylysine (PLL) by conjugating a small molecular imaging agent, fluorescent molecule and targeting agent amino phenylboronic acid onto the amino groups of polylysine, which can specifically target monosaccharide sialic acid residues overexpressing on the surface of tumor cell membranes. Further, 3,4,5,6-Tetrahydrophthalic anhydride (DCA) was attached to the free amino groups of the polylysine to change to a negative charge at physiology pH to lower the cytotoxicity, but it soon regenerated to a positive charge again once reaching the acidic intratumoral environment and therefore increased cell uptake. Laser confocal microscopy images showed that most of the polymeric contrast agents were bound to the cancer cell membrane. Moreover, the tumor targeting contrast agent showed the same magnetic resonance imaging (MRI) contrasting performance in vitro as the small molecule contrast agent used in clinic, which made it a promising tumor-targeting polymeric contrast agent for cancer diagnosis.
我们通过将小分子成像剂、荧光分子和靶向剂氨基苯硼酸连接到聚赖氨酸的氨基上，开发了一种基于线性聚赖氨酸 (PLL) 的肿瘤靶向造影剂，该造影剂可以特异性地靶向肿瘤细胞膜表面过度表达的单糖唾液酸残基。此外，将 3,4,5,6-四氢邻苯二甲酸酐 (DCA) 连接到聚赖氨酸的游离氨基上，在生理 pH 下变为负电荷以降低细胞毒性，但一旦达到酸性肿瘤内环境，它很快又会重新变为正电荷，从而增加细胞摄取。激光共聚焦显微镜图像显示，大多数聚合物造影剂都与癌细胞膜结合。此外，肿瘤靶向造影剂在体外表现出与临床使用的小分子造影剂相同的磁共振成像 (MRI) 对比性能，使其成为一种有前途的用于癌症诊断的肿瘤靶向聚合物造影剂。
