Design of peptide–dendrimer conjugates with tumor homing and antitumor effects
Design of peptide–dendrimer conjugates with tumor homing and antitumor effects
复制标题
具有肿瘤归巢和抗肿瘤作用的肽-树枝状大分子缀合物的设计
DOI：
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
E. Kondo
中科院分区：
文献类型：
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作者：
C. Kojima;Ken Saito;E. Kondo
开发用于癌症治疗的药物输送系统是一个至关重要的问题。以前，一些多肽被设计为具有抗肿瘤活性的肿瘤归巢细胞穿透肽。本研究利用针对急性髓系白血病(AML)的肿瘤靶向CPP44多肽和抗肿瘤P16INK4a多肽设计了具有肿瘤靶向活性和抗肿瘤作用的双功能树枝状大分子。合成了两种类型的多肽-树枝状大分子偶联物。一种是CPP44连接的p16INK4a多肽连接的树状大分子(串联连接的树枝状大分子)，另一种是CPP44和p16INK4a多肽连接的树状大分子(平行连接的树枝状大分子)。此外，将组织蛋白酶B底物连接到抗肿瘤p16INK4a多肽上，将其从载体中释放出来。这些多肽-树枝状大分子结合物比CPP44连接的p16INK4a多肽产生更有效的抗肿瘤作用。与串联连接的树突状分子相比，平行连接的树状分子与AML细胞的关联性较小，但具有更强的抗肿瘤作用。这表明，细胞摄取和抗肿瘤多肽切割都影响双功能多肽偶联树突状大分子的抗肿瘤活性。
Development of drug delivery systems for cancer therapy is a crucial issue. Previously, some peptides were designed as tumor homing cell-penetrating peptides with antitumor activities. In this study, dual function dendrimers with tumor targeting activities and antitumor effects were designed using the tumor targeting CPP44 peptide for acute myelogenous leukemia (AML) and the antitumor p16INK4a peptide. Two types of peptide–dendrimer conjugates were synthesized. One was a CPP44-linked p16INK4a peptide-conjugated dendrimer (tandem linked dendrimer) and the other was a dendrimer conjugated with separate CPP44 and p16INK4a peptides (parallel linked dendrimer). In addition, a peptide cathepsin B substrate was linked to the antitumor p16INK4a peptide to release it from the carriers. These peptide–dendrimer conjugates produced more effective antitumor effects than a CPP44-linked p16INK4a peptide. The parallel linked dendrimer showed less association with AML cells than the tandem linked dendrimer, but had greater antitumor effects. This suggested that both cellular uptake and antitumor peptide cleavage affected the antitumor activities of dual functional peptide-conjugated dendrimers.
影响因子：
16.6
作者：
Riehemann, Kristina;Schneider, Stefan W.;Luger, Thomas A.;Godin, Biana;Ferrari, Mauro;Fuchs, Harald
通讯作者：
Fuchs, Harald