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Varna Medical Forum

Aspects Of The Use Of RGD Peptides

Momchil Lambev, Antonia Hristova, Dimana Dimitrova, Silvia Mihaylova, Stefka Valcheva-Kuzmanova, Tamara Pajpanova


The amino acid sequence L-argininyl-glycyl-L-asparaginic acid (RGD) is inherent in many extracellular and intracellular proteins. Initially, the RGD peptide was identified in fibronectin in 1984 by E. Ruoslahti, who found that these three amino acids were the site of adhesion of cells to the extracellular matrix or other cells by cell adhesion molecules as integrins. Subsequently, this tri-amino acid residue was also found in many other proteins in the extracellular matrix and blood. It is a common pattern of recognition by some cell receptors. Following the discovery of the RGD sequence as a potential ligand for binding to cellular integrins (most commonly αvβ3), RGD-mediated small molecules and RGD-containing therapeutic peptides and proteins have been used for controlled drug distribution and as agents for cell targeting and endosomal delivery. Due to the large number of integrins in endothelial cells and blood vessels to tumor tissues, RGD-mediated drug delivery is of a particular interest in cancer therapy. Furthermore, the RGD-integrin system is used for target cell recognition and internalization, which is applied to human-created structures that mimic pathogens. Because of this, the systems are being tested for use as diagnostics, therapeutics, and regenerating transplanted tissues.

The detection of tumors is characterized by high specificity and sensitivity by conjugation of markers with RGD peptides. This important technology is widely used for early diagnosis and differential diagnosis of tumors as well as for clinical analysis and treatment. RGD-modified drugs and imaging agents have been created by conjugation of RGD peptides to carriers. The carrier molecules are loaded with drug molecules or signal-generating molecules. RGD peptides and RGD mimetics are also applied to modify liposomes, polymers and peptides in a chemical way that increases their biological effects as therapeutic agents.

RGD peptides are promising molecules with great future use in therapy as a drug-delivery system, in imaging diagnostics and in tissue engineering.


RGD peptides; anticancer therapy; drug delivery; imaging diagnostics; tissue engineering

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Aguzzi MS, Giampietri C, De Marchis F, Padula F, Gaeta R, Ragone G, Capogrossi M and Facchiano A. RGDS peptide induces caspase 8 and caspase 9 activation in human endothelial cells. Blood 2004;103:4180-4187.

Balacheva A, Iliev I, Detcheva R, Dzimbova T, Pajpanova T, Golovinsky E. In vitro assessment of the cytotoxic effects of novel RGD analogues. BioDiscovery 2012 4(1)

Beer AJ, Schwaiger M. Imaging of integrin alpha v beta3 expression. Cancer Metastasis Rev. 2008;27:631-644.

Bellis SL. Advantages of RGD peptides for directing cell association with biomaterials. Biomaterials 2011;32:4205-4210.

Bouzin C, Feron O. Targeting tumor stroma and exploiting mature tumor vasculature to improve anti-cancer drug delivery. Drug Resist. Updates 2007;10:109−120.

Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv. Drug Delivery Rev. 2008;60:1615−1626.

Chen J, Bly R, Saad, M, AlKhodary M, El-Backly R, Cohen D, Kattamis N, Fatta M, Moore W, Arnold C. In vivo study of adhesion and bone growth around implanted laser groove/RGD-functionalized Ti-6Al-4V pins in rabbit femurs. Mat.Sci.Eng. C 2011;31:826–832.

Colombo M, Bianchi A. Click chemistry for the synthesis of RGD-containing integrin ligands. Molecules 2010;15:178–197

Danhier F, Le Breton A, and Preat V. RGD-Based Strategies To Target Alpha(v) Beta(3) Integrin in Cancer Therapy and Diagnosis. Mol. Pharmaceutics 2012;9:2961−2973

Daniels TR, Delgado T, Helguera G, Penichet ML. The transferrin receptor part II: targeted delivery of therapeutic agents into cancer cells. Clin. Immunol. 2006;121(2):159−176.

Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat. Rev. Cancer 2010;10:9−22.

Folkman J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 1971;285:1182−1186.

García AJ. Get a grip: Integrins in cell-biomaterial interactions. Biomaterials 2005;26:7525–7529.

Gil ES, Mandal BB, Park SH, Marchant JK, Omenetto FG, Kaplan DL. Helicoidal multi-lamellar features of RGD-functionalized silk biomaterials for corneal tissue engineering. Biomaterials 2010;31:8953–8963.

Haubner R, Wester HJ. Radiolabeled tracers for imaging of tumor angiogenesis and evaluation of anti-angiogenic therapies. Curr. Pharm. Design. 2004;10:1439–1455.

Jo DH, Lee TG, Kim JH. Nanotechnology and nanotoxicology in retinopathy. Int. J. Mol. Sci. 2011;12:8288–8301

Kim J, Nam HY, Kim TI, Kim PH, Ryu J, Yun CO, Kim SW. Active targeting of RGD-conjugated bioreducible polymer for delivery of oncolytic adenovirus expressing shRNA against IL-8 mRNA. Biomaterials 2011;32:5158–5166.

Maeda H, Sawa T, Konno T. Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. J. Controlled Release 2001;74:47−61.

Malam Y, Loizidou M, Seifalian AM. Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer. Trends Pharmacol. Sci. 2009;30:592−599.

Misra R, Acharya S, Sahoo SK. Cancer nanotechnology: application of nanotechnology in cancer therapy. Drug Discovery Today 2010;15:842−850.

Pierschbacher MD, Ruoslahti E. Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature 1984;309:30–33.

Shachar M, Tsur-Gang O, Dvir T, Leor J, Cohen S. The effect of immobilized RGD peptide in alginate scaffolds on cardiac tissue engineering. Acta Biomater. 2011;7:152–162.

Temming K, Schiffelers RM, Molema G, Kok RJ. RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature. Drug Resist. Update 2005;8:381–402.

Ung P, Winkler DA. Tripeptide Motifs in Biology: Targets for Peptidomimetic Design J Med Chem 2011;54:1111–1125

Wang F, Li Y, Shen Y, Wang A, Wang S and Xie T. The Functions and Applications of RGD in Tumor Therapy and Tissue Engineering. Int. J. Mol. Sci. 2013;14:13447-13462

Ye Y, Chen X. Integrin targeting for tumor optical imaging. Theranostics 2011;1:103−125.

Zheng W, Wang Z, Song L, Zhao Q, Zhang J, Li D, Wang S, Han J, Zheng XL, Yang Z. Endothelialization and patency of RGD-functionalized vascular grafts in a rabbit carotid artery model. Biomaterials 2012;33:2880–2891.

Zitzmann S, Ehemann V, Schwab M. Arginine-glycineaspartic acid (RGD)-peptide binds to both tumor and tumorendothelial cells in vivo. Cancer Res. 2002;62:5139−5143



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