Design, synthesis and bioevaluation of an EphA2 receptor-based targeted delivery system.
Design, synthesis and bioevaluation of an EphA2 receptor-based targeted delivery system.
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DOI：
10.1002/cmdc.201400067
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发表时间：
2014-07
期刊：
影响因子：
3.4
通讯作者：
Pellecchia, Maurizio
中科院分区：
文献类型：
--
作者：
Barile, Elisa;Wang, Si;Das, Swadesh K.;Noberini, Roberta;Dahl, Russell;Stebbins, John L.;Pasquale, Elena B.;Fisher, Paul B.;Pellecchia, Maurizio
我们最近描述了一种新的靶向递送系统，其基于与化疗剂紫杉醇缀合的特异性EphA 2受体靶向肽。在这篇手稿中，我们调查的化学决定因素负责这些药物在血浆中的稳定性和降解。在肽和肽与紫杉醇之间的接头两者中引入修饰，导致药物缀合物在大鼠血浆中均长寿命，并且与紫杉醇单独治疗相比，在前列腺癌异种移植模型中显著减小肿瘤大小。这些研究确定了肽-药物缀合物上的关键限速降解位点，从而能够设计具有增加的稳定性和功效的药剂。这些结果为我们的中心假设提供了支持，即靶向EphA 2受体的肽-药物缀合物代表了选择性地将细胞毒性药物递送至癌细胞的创新且潜在有效的策略。
We recently described a new targeted delivery system based on specific EphA2 receptor targeting peptides conjugated with the chemotherapeutic agent paclitaxel. In this manuscript we investigate the chemical determinants responsible for the stability and degradation of these agents in plasma. Introducing modifications in both the peptide and the linker between the peptide and paclitaxel, resulted in drug conjugates that are both long-lived in rat plasma and that markedly reduced tumor size in a prostate cancer xenograft model compared to paclitaxel alone treatment. These studies identify critical rate-limiting degradation sites on the peptide-drug conjugates, enabling the design of agents with increased stability and efficacy. These results provide support for our central hypothesis that peptide-drug conjugates targeting the EphA2 receptor represent an innovative and potentially effective strategy to selectively deliver cytotoxic drugs to cancer cells.
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影响因子：
11.2
作者：
Jackson, Dowdy;Gooya, John;Tice, David A.
通讯作者：
Tice, David A.
影响因子：
3.4
作者：
Annunziata, Christina M;Kohn, Elise C;LoRusso, Patricia;Houston, Nicole D;Coleman, Robert L;Buzoianu, Manuela;Robbie, Gabriel;Lechleider, Robert
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Lechleider, Robert
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50.3
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通讯作者：
Vescovi AL
影响因子：
3.6
作者：
Margaryan NV;Strizzi L;Abbott DE;Seftor EA;Rao MS;Hendrix MJ;Hess AR
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Hess AR
影响因子：
3.6
作者：
Merritt, William M.;Thaker, Premal H.;Sood, Anil K.
通讯作者：
Sood, Anil K.