RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature |
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Authors: | Kai Temming Raymond M Schiffelers Grietje Molema Robbert J Kok |
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Institution: | Department of Pharmacokinetics and Drug Delivery, Groningen University Institute for Drug Exploration (GUIDE), Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands. |
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Abstract: | 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. |
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Keywords: | Arg-Gly-Asp RGD Endothelial cells Angiogenesis Antivascular therapies Cancer Drug delivery Gene delivery Therapeutic proteins Polymers Cytostatic drugs Radiotracer |
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