In vitro synergistic action of geldanamycin- and docetaxel-containing HPMA copolymer-RGDfK conjugates against ovarian cancer.
In vitro synergistic action of geldanamycin- and docetaxel-containing HPMA copolymer-RGDfK conjugates against ovarian cancer.
复制标题
Geldanamycin和含有多西他赛的HPMA共聚物RGDFK偶联的体外协同作用与卵巢癌。
DOI：
10.1002/mabi.201400360
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发表时间：
2014-12
影响因子：
4.6
通讯作者：
Ghandehari, Hamidreza
中科院分区：
文献类型：
--
作者：
Larson, Nate;Roberts, Sarah;Ray, Abhijit;Buckway, Brandon;Cheney, Darwin L.;Ghandehari, Hamidreza
本研究描述了利用HPMA共聚物-RGDfK缀合物的组合疗法的合成、表征和体外评价。合成并表征了带有氨基己基格尔德霉素或多西他赛的HPMA共聚物-RGDfK缀合物。在生理学相关介质中评价稳定性。评估与卵巢癌细胞表面上的αvβ3整联蛋白的结合。评估了对卵巢癌细胞的细胞毒性，并通过组合指数分析评估了结合物组合诱导细胞死亡的能力。携带氨基己基格尔德霉素的缀合物比携带多西他赛的缀合物更稳定，并且表现出更慢的药物释放。两种偶联物均表现出特异性结合αvβ3整联蛋白的能力。在组合中，HPMA共聚物-RGDfK缀合物与其非靶向对应物和游离药物对照相比表现出显著的协同作用。HPMA共聚物-RGDfK缀合物轴承aminohexylgeldanamycin和多西他赛在体外诱导细胞毒性的协同方式，表明其作为一个有前途的联合治疗卵巢癌的潜力。
This study describes the synthesis, characterization, and in vitro evaluation of a combination therapy utilizing HPMA copolymer-RGDfK conjugates. HPMA copolymer-RGDfK conjugates bearing either aminohexylgeldanamycin or docetaxel were synthesized and characterized. Stability was evaluated in physiologically relevant media. Binding to αvβ3 integrins on the surface of ovarian cancer cells was assessed. Cytotoxicity towards ovarian cancer cells was evaluated and the ability of the conjugates in combination to induce cell death was assessed by combination index analysis. Conjugates bearing aminohexylgeldanamycin were more stable and exhibited slower drug release than those bearing docetaxel. Both conjugates demonstrated the ability to bind specifically to αvβ3 integrins. In combination, HPMA copolymer-RGDfK conjugates demonstrated marked synergism as compared to their non-targeted counterparts and free drug controls. HPMA copolymer-RGDfK conjugates bearing aminohexylgeldanamycin and docetaxel induce cytotoxicity in vitro in a synergistic manner, suggesting their potential as a promising combination therapy for ovarian cancer.
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影响因子：
3.6
作者：
Belfiglio, Maurizio;Fanizza, Caterina;Tinari, Nicola;Ficorella, Corrado;Iacobelli, Stefano;Natoli, Clara
通讯作者：
Natoli, Clara
影响因子：
4.9
作者：
Borgman MP;Aras O;Geyser-Stoops S;Sausville EA;Ghandehari H
通讯作者：
Ghandehari H
影响因子：
2.7
作者：
Gamble LJ;Borovjagin AV;Matthews QL
通讯作者：
Matthews QL
影响因子：
4.7
作者：
Fu S;Hennessy BT;Ng CS;Ju Z;Coombes KR;Wolf JK;Sood AK;Levenback CF;Coleman RL;Kavanagh JJ;Gershenson DM;Markman M;Dice K;Howard A;Li J;Li Y;Stemke-Hale K;Dyer M;Atkinson E;Jackson E;Kundra V;Kurzrock R;Bast RC Jr;Mills GB
通讯作者：
Mills GB
影响因子：
4.7
作者：
Gadducci, A;Sartori, E;Cristofani, R
通讯作者：
Cristofani, R