Curb challenges of the "Trojan Horse" approach: smart strategies in achieving effective yet safe cell-penetrating peptide-based drug delivery.
Curb challenges of the "Trojan Horse" approach: smart strategies in achieving effective yet safe cell-penetrating peptide-based drug delivery.
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DOI：
10.1016/j.addr.2012.11.007
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发表时间：
2013-10
影响因子：
16.1
通讯作者：
Yang, Victor C.
中科院分区：
文献类型：
--
作者：
Huang, Yongzhuo;Jiang, Yifan;Wang, Huiyuan;Wang, Jianxin;Shin, Meong Cheol;Byun, Youngro;He, Huining;Liang, Yanqin;Yang, Victor C.
细胞穿透肽(CPP)介导的细胞内药物传递系统，通常被称为“特洛伊木马途径”，已成为实现蛋白质、DNA、siRNAs和药物载体等大分子化合物有效传递的“圣杯”。它的特点是具有独特的细胞(或受体)、温度和有效载荷不依赖的机制，因此提供了有效的手段来改善细胞对各种大分子药物的摄取不足。然而，这种特洛伊木马方法也像一把双刃剑，由于缺乏强大的细胞穿透活性的靶点选择性，对体内应用的正常组织或器官造成了严重的安全和毒性问题。为了克服这种有效而非选择性的渗透与靶向递送的问题，近年来已经开发了许多“智能”策略，包括基于各种刺激响应机制的可控CPP药物递送系统。这篇综述文章提供了对这些智能系统的基本了解，并讨论了它们在体内的实时适用性。
Cell-penetrating peptide (CPP)-mediated intracellular drug delivery system, often specifically termed as “the Trojan horse approach”, has become the “holy grail” in achieving effective delivery of macromolecular compounds such as proteins, DNA, siRNAs, and drug carriers. It is characterized by the unique cell- (or receptor-), temperature-, and payload-independent mechanisms, therefore offering potent means to improve poor cellular uptake of a variety of macromolecular drugs. Nevertheless, this “Trojan horse” approach also acts like a double-edged sword, causing serious safety and toxicity concerns to normal tissues or organs for in vivo application, due to lack of target selectivity of the powerful cell penetrating activity. To overcome this problem of potent yet non-selective penetration vs. targeting delivery, a number of “smart” strategies have been developed in recent years, including controllable CPP-based drug delivery systems based on various stimuli-responsive mechanisms. This review article provides a fundamental understanding of these smart systems, as well as a discussion of their real-time in vivo applicability.
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影响因子：
3.8
作者：
Dietz, GPH;Bähr, M
通讯作者：
Bähr, M
影响因子：
3.5
作者：
Dietz, GPH;Kilic, E;Bähr, M
通讯作者：
Bähr, M
影响因子：
4.9
作者：
Gullotti E;Yeo Y
通讯作者：
Yeo Y
影响因子：
14
作者：
Choi, Jin Kyu;Jang, Ji-Hye;Park, Jin Woo
通讯作者：
Park, Jin Woo
DOI：
10.1073/pnas.97.8.3884
发表时间：
2000-04-11
影响因子：
11.1
作者：
Fang, JM;Shing, Y;Moses, MA
通讯作者：
Moses, MA