Department of Chemistry, The Vanderbilt Institute for Chemical Biology and Vanderbilt-Ingram Cancer Center, Vanderbilt University, VU Station B 351822 Nashville, Tennessee 37235-1822, USA.
Bioconjug Chem. 2009 Nov;20(11):2082-9. doi: 10.1021/bc9002053.
While it has become common practice for dendrimers to deliver imaging and therapeutic agents, there are few reported examples of cellular internalization of dendrimers. Moreover, targeting of dendrimers to the mitochondria in cells has not yet been reported. Previously, we have delivered small molecule imaging agents into glioma and breast cancer cells by targeting the translocator protein (TSPO; formerly known as the peripheral benzodiazepine receptor or PBR) with a family of high-affinity conjugable ligands. The 18 kDa multimeric TSPO is expressed in steroid-producing cells, primarily on the outer mitochondrial membrane. This protein is a prime candidate for molecular targeting because tumors and other disease-related cells contain high densities of TSPO. Here, we present the synthesis, characterization, and cellular internalization into C6 rat glioma cells of a TSPO targeted dendrimer imaging agent.
虽然将树枝状大分子用于递呈成像和治疗剂已成为常见做法，但很少有关于树枝状大分子被细胞内化的报道。此外，将树枝状大分子靶向递送至细胞内的线粒体也尚未见报道。之前，我们通过使用一组高亲和力可连接配体靶向转运蛋白（TSPO；以前称为外周苯二氮䓬受体或 PBR），将小分子成像剂递送至神经胶质瘤和乳腺癌细胞。分子量为 18 kDa 的多聚 TSPO 表达于甾体生成细胞，主要位于线粒体外膜。这种蛋白是分子靶向的首选候选物，因为肿瘤和其他与疾病相关的细胞中含有高密度的 TSPO。在这里，我们展示了一种针对 TSPO 的树枝状大分子成像剂的合成、表征以及进入 C6 大鼠神经胶质瘤细胞的内化情况。
