Description: The main limit of the anticancer agents is the non-specific action on the healthy cells limiting the dosages that can be applied and leading to serious side-effects. In this context, targeted delivery systems allow the selective entry of drugs into the primary tumor, as well as at the site of metastasis. Targeted drug approach is achieved by the exploitation of molecular markers that are over-expressed in cancerous tissues. In particular, ? v? 3 integrin is highly expressed on some invasive as well as the new-born blood vessel. The expression level of the integrin? v? 3, indeed, is an important factor in determining the invasiveness and metastatic potential of malignancy in both preclinical animal models and cancer patients. In this framework the research activity at IBB is focused on the development of peptide based antagonists able to selectively recognize? v? 3 integrin and to deliver radionuclides and/or cytotoxic molecules into tumor cells for therapeutic and/or diagnostic purposes. In parallel, new stabilised nanostructures opportunely functionalised with? v? 3 antagonists are also under investigation
Selected papers: Santulli G, Basilicata MF, De Simone M, Del Giudice C, Anastasio A, Sorriento D, Saviano M, Del Gatto A, Trimarco B, Pedone C, Zaccaro L, Iaccarino G. Evaluation of the anti-angiogenic properties of the new selective? V? 3 integrin antagonist RGDechiHCit J Transl Med. 2011, 9: 7. A. Zannetti, S. Del Vecchio, F. Iommelli, A. Del Gatto, S. De Luca, L. Zaccaro, A. Papaccioli, J. Sommella, M. Panico, A. Speranza, P. Grieco, E. Novellino, M. Saviano, C. Pedone and M. Salvatore Imaging of alphavbeta3 expression by a bifunctional chimeric RGD peptide not cross-reacting with alphavbeta5 Clin Cancer Res. , 2009, 15, 5224-33. L. Zaccaro, A. Del Gatto, C. Pedone and M. Saviano Peptides for Tumour Therapy and Diagnosis: Current Status and Future Directions Current Medicinal Chemistry, 2009, 16, 780-95L. Zaccaro, A. Del Gatto, C. Pedone and M. Saviano Integrin receptor family: promising target for therapeutic and diagnostic applications Current Topics in Biochemical Research, 2007, 9, 45-56. A. Del Gatto, L. Zaccaro, P. Grieco, E. Novellino, A. Zannetti, S. Del Vecchio, F. Iommelli, M. Salvatore, C. Pedone, M. Saviano Novel and Selective alpha (v) beta (3) Receptor Peptide Antagonist: Design, Synthesis, and Biological Behavior J. Med. Chem. 2006, 49, 3416-3420
Targeted Drug Delivery by integrin avb3 antagonist