Therapeutic Applications of Cell-Penetrating Peptides
Therapeutic Applications of Cell-Penetrating Peptides
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DOI：
10.1007/978-1-60761-919-2_38
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Maclean, Derek
中科院分区：
文献类型：
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作者：
Johnson, Randolph M.;Harrison, Stephen D.;Maclean, Derek
自从 15 年前发现具有穿过质膜能力的蛋白质转录因子以来，人们一直在评估细胞穿透肽 (CPP) 将不同物质转运至细胞、组织和器官的能力。某些 CPP 已被用于细胞内传递富含信息的分子，以调节蛋白质相互作用，从而抑制疾病的关键细胞机制。将药物引入细胞的能力允许改变药物的常规生物分布，从而对毒性、患者依从性和其他治疗因素产生有利影响。在本专着中，我们介绍了 CPP 在人类治疗开发中应用的现状和未来前景。我们讨论了在体内使用 CPP 的一些优点和缺点，并回顾了许多 CPP 介导的治疗递送的临床前和人体临床研究的现状。其中包括 CPP 缀合部分，针对越来越多的靶标和疾病领域，包括癌症、心脏病、疼痛和中风。我们的讨论重点是那些已在人体中进行测试的疗法，包括用于治疗急性心肌梗塞的 CPP 结合物。许多这些研究中获得的有希望的结果表明，CPP 可能在新型疗法的开发中发挥重要作用。
Since the discovery over 15 years ago of a protein transcription factor that possessed the ability to cross the plasma membrane, cell-penetrating peptides (CPPs) have been evaluated for the ability to transport diverse cargoes into cells, tissues, and organs. Certain CPPs have been used for the intracellular delivery of information-rich molecules to modulate protein protein interactions and thereby inhibit key cellular mechanisms of disease. The ability to introduce drugs into cells allows the conventional biodistribution of drugs to be altered in order to favorably impact toxicity, patient compliance, and other treatment factors.In this monograph, we present the current status and future prospects for the application of CPPs to the development of human therapeutics. We discuss some of the advantages and disadvantages of using CPPs in the in vivo setting, and review the current status of a number of preclinical and human clinical studies of CPP-mediated delivery of therapeutics. These include CPP-conjugated moieties directed against a growing variety of targets and disease areas, including cancer, cardiology, pain, and stroke. Our discussion focuses on those therapeutics that have been tested in humans, including a CPP conjugate for the treatment of acute myocardial infarction. The promising results obtained in a number of these studies indicate that CPPs may have an important role in the development of novel therapeutics.