title: αvβ3 Integrin-Targeted Peptide/Peptidomimetic-Drug Conjugates: In-Depth Analysis of the Linker Technology.
abstract: 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.
authors.forename: Alberto
authors.initials: A
authors.lastname: Dal Corso
authors.forename: Luca
authors.initials: L
authors.lastname: Pignataro
authors.affiliation: Universita degli Studi di Milano, Dipartimento di Chimica, via C. Golgi, 19, I-20133, Milan (Italy). laura.belvisi@unimi.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Belvisi
authors.forename: Cesare
authors.initials: C
authors.lastname: Gennari
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism*; D057786:Peptidomimetics
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D057786:Peptidomimetics; C047981:arginyl-glycyl-aspartic acid