Temming Kai, Schiffelers Raymond M, Molema Grietje, Kok Robbert J
Department of Pharmacokinetics and Drug Delivery, Groningen University Institute for Drug Exploration (GUIDE), Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Drug Resist Updat. 2005 Dec;8(6):381-402. doi: 10.1016/j.drup.2005.10.002. Epub 2005 Nov 23.
During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to alphavbeta3-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to couple RGD-peptides and RGD-mimetics to liposomes, polymers, peptides, small molecule drugs and radiotracers. Some of these products show impressive results in preclinical animal models and a RGD targeted radiotracer has already successfully been tested in humans for the visualization of alphavbeta3-integrin, which demonstrates the feasibility of this approach. This review will summarize the structural requirements for RGD-peptides and RGD-mimetics as ligands for alphavbeta3. We will show how they have been introduced in the various types of constructs by chemical and recombinant techniques. The importance of multivalent RGD-constructs for high affinity binding and internalization will be highlighted. Furthermore the in vitro and in vivo efficacy of RGD-targeted therapeutics and diagnostics reported in recent years will be reviewed.
在过去十年中，RGD肽已成为一种将药物和成像剂靶向表达αvβ3整合素的肿瘤脉管系统的常用工具。RGD肽已通过重组手段引入治疗性蛋白质和病毒中。化学方法已被用于将RGD肽和RGD模拟物偶联到脂质体、聚合物、肽、小分子药物和放射性示踪剂上。其中一些产品在临床前动物模型中显示出令人印象深刻的结果，并且一种RGD靶向放射性示踪剂已在人体中成功进行了测试，用于αvβ3整合素的可视化，这证明了该方法的可行性。本综述将总结RGD肽和RGD模拟物作为αvβ3配体的结构要求。我们将展示它们是如何通过化学和重组技术引入各种类型的构建体中的。将强调多价RGD构建体对于高亲和力结合和内化的重要性。此外，还将综述近年来报道的RGD靶向治疗和诊断的体外和体内疗效。
