1. Tumor Targeting with an isoDGR-Drug Conjugate.
- Author
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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, and Gennari, Cesare
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CONJUGATE addition reactions , *CONJUGATED polymers , *PACLITAXEL , *CANCER cells , *INTEGRINS - Abstract
Herein we report the first example of an isoDGR-drug conjugate ( 2), designed to release paclitaxel selectively within cancer cells expressing integrin αVβ3. 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 αVβ3 receptor (IC50=11.0 n m). 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 αVβ3 expression: human glioblastoma U87 (αVβ3+) and U87 β3-KO (αVβ3−). 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). [ABSTRACT FROM AUTHOR]
- Published
- 2017
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