Tumor Targeting with an isoDGR–Drug Conjugate. Issue 33 (26th May 2017)

• Record Type: Journal Article
• Authors: Zanella, Simone; Angerani, Simona; Pina, Arianna; López Rivas, Paula; Giannini, Clelia; Panzeri, Silvia; Arosio, Daniela; Caruso, Michele; Gasparri, Fabio; Fraietta, Ivan; Albanese, Clara; Marsiglio, Aurelio; Pignataro, Luca; Belvisi, Laura; Piarulli, Umberto; Gennari, Cesare
• Is Part Of: Chemistry. Volume 23:Issue 33(2017)
• Page Start: 7910
• Page End: 7914
• Publication Date: 2017-05-26
• Subjects: antitumor agents -- cancer -- drug delivery -- integrins -- peptidomimetics; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201701844
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Herein we report the first example of an iso DGR–drug conjugate (2 ), designed to release paclitaxel selectively within cancer cells expressing integrin αV β3 . Conjugate2 was synthesized by connecting the iso DGR peptidomimetic5 with paclitaxel via the lysosomally cleavable Val–Ala dipeptide linker. Conjugate2 displayed a low nanomolar affinity for the purified integrin αV β3 receptor (IC50 =11.0 nm ). The tumor targeting ability of conjugate2 was assessed in vitro in anti‐proliferative assays on two isogenic cancer cell lines characterized by different integrin αV β3 expression: human glioblastoma U87 (αV β3 +) and U87 β3 ‐KO (αV β3 −). The iso DGR‐PTX conjugate2 displayed a remarkable targeting index (TI=9.9), especially when compared to the strictly related RGD‐PTX conjugate4 (TI=2.4). Abstract : Hitting bullseye : The skillful marksman ( iso DGR–drug conjugate) targets cancer cells expressing integrin αV β3, and releases the warhead (paclitaxel) selectively into them.