Anticancer activity of proapoptotic peptides is highly improved by thermal targeting using elastin-like polypeptides.
Anticancer activity of proapoptotic peptides is highly improved by thermal targeting using elastin-like polypeptides.
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DOI：
10.1007/s10989-012-9295-y
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发表时间：
2012-09
影响因子：
2.5
通讯作者：
Raucher D
中科院分区：
文献类型：
--
作者：
Moktan S;Raucher D
诱导癌细胞凋亡是肿瘤治疗的有效策略。已知形成KLAK多肽的阳离子α-螺旋(KLAK)通过破坏线粒体诱导细胞凋亡。在本研究中，我们设计了一种热靶向Klak多肽，方法是将Klak序列改造到热响应性生物聚合物弹性蛋白样多肽(ELP)的羧基末端。ELP-KLAK的细胞内化是通过设计ELP氨基末端的穿透肽序列(SynB1)来实现的。SynB1-ELP1-KLAK融合多肽对雌激素受体阳性和阴性的人乳腺癌细胞株均具有细胞毒作用。加温治疗后，SynB1-ELP1-KLAK的效力进一步增强。作为对高温的反应，SynB1-ELP1-KLAK选择性地触发细胞凋亡，这与线粒体的破坏有关。热响应性SynB1-ELP-Klak多肽可以通过应用温和热疗来改善肿瘤靶向性。此外，ELP的药代动力学特性可以阻止KLAK在体内的降解，而SynB1的使用可以介导肿瘤细胞的摄取，从而增强KLAK的作用。
Inducing apoptosis in cancer cells is an effective strategy for cancer therapy. The cationic α-helix forming KLAKLAKKLAKLAK peptide (KLAK) has been known to induce apoptosis by disrupting the mitochondria. In the present study, we have designed a thermally targeted KLAK peptide by genetically engineering the KLAK sequence to the carboxy terminus of the heat responsive biopolymer elastin-like polypeptide (ELP). The cellular internalization of ELP-KLAK was made possible by engineering a cell penetrating peptide sequence (SynB1) to the amino terminus of ELP. The SynB1-ELP1-KLAK fusion polypeptide was cytotoxic against both estrogen receptor positive and negative human breast cancer cell lines. The potency of SynB1-ELP1-KLAK was further enhanced when mild hyperthermia was added to the treatment. In response to hyperthermia, SynB1-ELP1-KLAK selectively triggered apoptosis, which was associated with disruption of the mitochondria. The thermally responsive SynB1-ELP-KLAK polypeptide can have improved tumor targeting by the application of mild hyperthermia. Furthermore, the pharmacokinetic properties of ELP can prevent degradation of KLAK in vivo, and the use of SynB1 can mediate tumor cell uptake, thereby augmenting the effect of KLAK.
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影响因子：
41.2
作者：
通讯作者：
--
影响因子：
10.8
作者：
Furgeson, DY;Dreher, MR;Chilkoti, A
通讯作者：
Chilkoti, A
影响因子：
5.8
作者：
Bidwell, Gene L., III;Fokt, Izabela;Raucher, Drazen
通讯作者：
Raucher, Drazen
影响因子：
3.4
作者：
Moktan, Shama;Ryppa, Claudia;Raucher, Drazen
通讯作者：
Raucher, Drazen
影响因子：
16.1
作者：
Bidwell, Gene L., III;Raucher, Drazen
通讯作者：
Raucher, Drazen