Targeting RGD recognizing integrins: Drug development, biomaterial research, tumor imaging and targeting

Integrins constitute an important class of cell adhesion receptors responsible not only for cell-matrix adhesion but also for signaling bidirectionally across the membrane. Integrins are involved in many biological processes such as angiogenesis, thrombosis, inflammation, osteoporosis and cancer. Integrins thus play a key role in many severe human diseases. In this review we will describe recent research and development of RGD-containing integrin ligands for medical applications including drug design, radiolabeling, drug targeting, as well as biomaterial research. Many ligands have been developed for targeting the alpha v beta 3 integrin in order to block angiogenesis or osteoporosis, but there are also other integrins like alpha v beta 5 and alpha 5 beta 1 which become more and more interesting for similar purposes. alpha IIb beta 3 constitutes a potent target in thrombosis therapy; but the search for suitable ligands is still ongoing. We will reconstruct the drug development process for these integrin subtypes considering selected examples with focus on structure based design. Different structural requirements are pointed out concerning integrin activity and particularly the selectivity towards the distinct integrin types. Furthermore, we will show recent progress in tumor and thrombosis imaging based on radiolabeled RGD-containing ligands binding alpha v beta 3 or alpha IIb beta 3, respectively. Additionally further advances in biornaterial research are presented. We describe the coating of different implant materials with various alpha v beta 3 recognizing ligands for the purpose of increasing cell attachment and biocompatibility.