Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.
Protein Eng Des Sel. 2010 Jun;23(6):423-30. doi: 10.1093/protein/gzq011. Epub 2010 Feb 25.
Tumor-specific cytotoxicity of drugs can be enhanced by targeting them to tumor receptors using tumor-specific ligands. Phage display technology with its high throughput capacity for the analysis of targeting ligands possessing specific binding properties represents a very attractive tool in the quest for molecular ligands. Also, current phage nanobiotechnology concepts allow the use of intact phage particles and isolated phage coat proteins per se as components of nanomedicines. Herein, we describe the use of two landscape phage libraries to obtain phage ligands against PC3 prostate carcinoma cells. Following a very stringent selection scheme, we were able to identify three phage ligands, bearing the fusion peptides, DTDSHVNL, DTPYDLTG and DVVYALSDD that demonstrated specificity and selectivity to PC3 cells based on target-association assays, microscopy and flow cytometry. The phage ligands and their fusion coat proteins can be used as navigating modules in both therapeutic and diagnostic approaches to prostate carcinoma.
利用肿瘤特异性配体将药物靶向肿瘤受体可以增强其对肿瘤的细胞毒性。噬菌体展示技术以其对具有特定结合特性的靶向配体进行高通量分析的能力，成为寻找分子配体的极具吸引力的工具。此外，当前的噬菌体纳米生物技术概念允许使用完整的噬菌体颗粒和分离的噬菌体衣壳蛋白本身作为纳米药物的组成部分。本文描述了使用两种景观噬菌体文库来获得针对 PC3 前列腺癌细胞的噬菌体配体。在非常严格的选择方案之后，我们能够鉴定出三个噬菌体配体，它们携带融合肽 DTDSHVNL、DTPYDLTG 和 DVVYALSDD，基于靶标结合测定、显微镜和流式细胞术，这些噬菌体配体显示出对 PC3 细胞的特异性和选择性。噬菌体配体及其融合衣壳蛋白可用作前列腺癌治疗和诊断方法中的导航模块。
