Tumor Targeting with an isoDGR-Drug Conjugate

被引：18

作者：

Zanella, Simone ^{[1
]}

Angerani, Simona ^{[1
]}

Pina, Arianna ^{[1
]}

Rivas, Paula Lopez ^{[1
]}

Giannini, Clelia ^{[1
]}

Panzeri, Silvia ^{[2
]}

Arosio, Daniela ^{[3
]}

Caruso, Michele ^{[4
]}

Gasparri, Fabio ^{[4
]}

Fraietta, Ivan ^{[4
]}

Albanese, Clara ^{[4
]}

Marsiglio, Aurelio ^{[4
]}

Pignataro, Luca ^{[1
]}

Belvisi, Laura ^{[1
]}

Piarulli, Umberto ^{[2
]}

Gennari, Cesare ^{[1
]}

机构：

[1] Univ Milan, Dipartimento Chim, Via C Golgi 19, I-20133 Milan, Italy

[2] Univ Insubria, Dipartimento Sci & Alta Tecnol, Via Valleggio 11, I-22100 Como, Italy

[3] CNR, ISTM, Via C Golgi 19, I-20133 Milan, Italy

[4] Nerviano Med Sci, Via Pasteur 10, I-20014 Nerviano, Italy

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2017年 / 23卷 / 33期

关键词：

antitumor agents; cancer; drug delivery; integrins; peptidomimetics; BIFUNCTIONAL DIKETOPIPERAZINE SCAFFOLDS; PEPTIDE-PACLITAXEL CONJUGATE; BIOLOGICAL EVALUATION; RGD PEPTIDOMIMETICS; CYCLIC ISODGR; INTEGRIN; ALPHA(V)BETA(3); DESIGN; ISOASPARTATE; DELIVERY;

D O I：

10.1002/chem.201701844

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Herein we report the first example of an isoDGR-drug conjugate (2), designed to release paclitaxel selectively within cancer cells expressing integrin alpha(V)beta(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 alpha(V)beta(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 alpha(V)beta(3) expression: human glioblastoma U87 (alpha(V)beta(3) +) and U87 beta(3)-KO (alpha(V)beta(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).

引用

页码：7910 / 7914

页数：5

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