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αvβ3 Integrin-Targeted Peptide/Peptidomimetic-Drug Conjugates: In-Depth Analysis of the Linker Technology

[ Vol. 16 , Issue. 3 ]


Alberto Dal Corso, Luca Pignataro, Laura Belvisi and Cesare Gennari   Pages 314 - 329 ( 16 )


Covalent conjugation of anticancer drugs to targeting carriers (e.g., antibodies or small molecules) capable of selectively binding to tumor-specific antigens, is emerging as a successful strategy to overcome the drawbacks of traditional chemotherapy. Due to its overexpression on blood vessels of human tumors, αvβ3 integrin is one of the most studied receptors of tumor-targeted therapeutics: several peptides and peptidomimetics, bearing the RGD (Arg-Gly-Asp) recognition sequence, have been developed as integrin ligands and linked to different anticancer drugs. The resulting integrin- targeted small molecule-drug conjugates (SMDCs) are able to release the cytotoxic agents upon cleavage of a linker under specific conditions (i.e., hydrolysis, enzymatic action or reduction). Despite the significant efforts made in this field, αvβ3 integrin-targeted SMDCs are still far from the clinic. In this review, we survey this approach with a special focus on the different linkers employed and the reported biological activities in vitro and in vivo.


Anticancer Prodrugs, Drug Targeting, Integrins, Peptidomimetics, RGD, Small Molecule-Drug Conjugates.


Universita degli Studi di Milano, Dipartimento di Chimica, via C. Golgi, 19, I-20133, Milan (Italy).

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