Legumain protease-activated TAT-liposome cargo for targeting tumours and their microenvironment
Legumain protease-activated TAT-liposome cargo for targeting tumours and their microenvironment
复制标题
Legumain 蛋白酶激活的 TAT 脂质体货物用于靶向肿瘤及其微环境
DOI：
10.1038/ncomms5280
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发表时间：
2014-06-01
影响因子：
16.6
通讯作者：
Xiang, Rong
中科院分区：
文献类型：
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作者：
Liu, Ze;Xiong, Min;Xiang, Rong
特异性靶向和细胞内化是抗肿瘤治疗剂载体的关键特性。在这里，我们开发了一种药物载体，通过连接的底物内切蛋白酶豆荚蛋白，丙氨酸-丙氨酸-天冬酰胺（AAN），细胞穿透肽（达特，反式激活因子）。AAN部分添加到达特中的第四个赖氨酸产生分支肽部分，这导致达特的跨膜转运能力降低72.65%。Legumain有效地催化TAT-脂质体从AAN-TAT-脂质体的释放，从而恢复达特的渗透能力。AAN-TAT-脂质体携带的多柔比星与对照递送系统携带的多柔比星相比，增加了多柔比星的杀肿瘤作用，降低了其全身不良反应。因此，这种递送平台的特异性靶向和高效率提供了一种新的方法来限制抗癌剂的毒性以及增加其在癌症治疗中的功效。
Specific targeting and cellular internalization are key properties for carriers of antitumor therapeutic agents. Here, we develop a drug carrier through the attachment of substrate of endoprotease legumain, alanine-alanine-asparagine (AAN), to cell-penetrating peptides (TAT, trans-activating factor). The addition of the AAN moiety to the fourth lysine in the TAT creates a branched peptide moiety, which leads to a decrease in the transmembrane transport capacity of TAT by 72.65%. Legumain efficiently catalyses the release of TAT-liposome from the AAN-TAT-liposome and thereby recovers the penetrating capacity of TAT. Doxorubicin carried by the AAN-TAT-liposome led to an increase in the tumoricidal effect of doxorubicin and a reduction in its systemic adverse effects in comparison with doxorubicin carried by a control delivery system. Thus, the specific targeting and high efficiency of this delivery platform offers a novel approach to limit the toxicity of anticancer agents as well as increasing their efficacy in cancer therapy.