Tumor Targeting with an isoDGR–Drug Conjugate

Herein we report the first example of an isoDGR–drug conjugate (2), designed to release paclitaxel selectively within cancer cells expressing integrin α(V)β(3). Conjugate 2 was synthesized by connecting the isoDGR peptidomimetic 5 with paclitaxel via the lysosomally cleavable Val–Ala dipeptide linke...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488297/
https://www.ncbi.nlm.nih.gov/pubmed/28449309
http://dx.doi.org/10.1002/chem.201701844
Descripción
Sumario:Herein we report the first example of an isoDGR–drug conjugate (2), designed to release paclitaxel selectively within cancer cells expressing integrin α(V)β(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 α(V)β(3) receptor (IC(50)=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 α(V)β(3) expression: human glioblastoma U87 (α(V)β(3)+) and U87 β(3)‐KO (α(V)β(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).

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