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Tumor Targeting with an isoDGR-Drug Conjugate.

ABSTRACT: Herein we report the first example of an isoDGR-drug conjugate (2), designed to release paclitaxel selectively within cancer cells expressing integrin ?_V ?₃ . Conjugate 2 was synthesized by connecting the isoDGR peptidomimetic 5 with paclitaxel via the lysosomally cleavable Val-Ala dipeptide linker. Conjugate 2 displayed a low nanomolar affinity for the purified integrin ?_V ?₃ receptor (IC₅₀ =11.0?nm). The tumor targeting ability of conjugate 2 was assessed in vitro in anti-proliferative assays on two isogenic cancer cell lines characterized by different integrin ?_V ?₃ expression: human glioblastoma U87 (?_V ?₃ +) and U87 ?₃ -KO (?_V ?₃ -). The isoDGR-PTX conjugate 2 displayed a remarkable targeting index (TI=9.9), especially when compared to the strictly related RGD-PTX conjugate 4 (TI=2.4).

SUBMITTER: Zanella S

PROVIDER: S-EPMC5488297 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Tumor Targeting with an isoDGR-Drug Conjugate.

Zanella Simone S Angerani Simona S Pina Arianna A López Rivas Paula P Giannini Clelia C Panzeri Silvia S Arosio Daniela D Caruso Michele M Gasparri Fabio F Fraietta Ivan I Albanese Clara C Marsiglio Aurelio A Pignataro Luca L Belvisi Laura L Piarulli Umberto U Gennari Cesare C

Chemistry (Weinheim an der Bergstrasse, Germany) 20170526 33

Herein we report the first example of an isoDGR-drug conjugate (2), designed to release paclitaxel selectively within cancer cells expressing integrin αV β3 . Conjugate 2 was synthesized by connecting the isoDGR peptidomimetic 5 with paclitaxel via the lysosomally cleavable Val-Ala dipeptide linker. Conjugate 2 displayed a low nanomolar affinity for the purified integrin αV β3 receptor (IC50 =11.0 nm). The tumor targeting ability of conjugat ...[more]

PMID: 28449309

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