Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
Iranian Comprehensive Hemophilia Care Center, Tehran, Iran.
Mol Biotechnol. 2023 Sep;65(9):1387-1402. doi: 10.1007/s12033-023-00679-1. Epub 2023 Jan 31.
Novel effective drugs or therapeutic vaccines have been already developed to eradicate viral infections. Some non-viral carriers have been used for effective drug delivery to a target cell or tissue. Among them, cell penetrating peptides (CPPs) attracted a special interest to enhance drug delivery into the cells with low toxicity. They were also applied to transfer peptide/protein-based and nucleic acids-based therapeutic vaccines against viral infections. CPPs-conjugated drugs or vaccines were investigated in several viral infections including poliovirus, Ebola, coronavirus, herpes simplex virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, Japanese encephalitis virus, and influenza A virus. Some studies showed that the uptake of CPPs or CPPs-conjugated drugs can be performed through both non-endocytic and endocytic pathways. Despite high potential of CPPs for cargo delivery, there are some serious drawbacks such as non-tissue-specificity, instability, and suboptimal pharmacokinetics features that limit their clinical applications. At present, some solutions are utilized to improve the CPPs properties such as conjugation of CPPs with targeting moieties, the use of fusogenic lipids, generation of the proton sponge effect, etc. Up to now, no CPP or composition containing CPPs has been approved by the Food and Drug Administration (FDA) due to the lack of sufficient in vivo studies on stability, immunological assays, toxicity, and endosomal escape of CPPs. In this review, we briefly describe the properties, uptake mechanisms, advantages and disadvantages, and improvement of intracellular delivery, and bioavailability of cell penetrating peptides. Moreover, we focus on their application as an effective drug carrier to combat viral infections.
已经开发出新型有效的药物或治疗性疫苗来消灭病毒感染。一些非病毒载体已被用于将有效药物递送到靶细胞或组织。其中，细胞穿透肽（CPPs）因其低毒性而引起了人们对增强药物向细胞内传递的特别关注。它们还被应用于传递基于肽/蛋白质和基于核酸的治疗性疫苗以对抗病毒感染。CPP 缀合物药物或疫苗已在包括脊髓灰质炎病毒、埃博拉病毒、冠状病毒、单纯疱疹病毒、人类免疫缺陷病毒、乙型肝炎病毒、丙型肝炎病毒、日本脑炎病毒和甲型流感病毒在内的几种病毒感染中进行了研究。一些研究表明，CPP 或 CPP 缀合物的摄取可以通过非内吞和内吞途径来完成。尽管 CPP 具有很高的货物传递潜力，但存在一些严重的缺点，如非组织特异性、不稳定性和不理想的药代动力学特征，限制了它们的临床应用。目前，一些解决方案被用于改善 CPP 的特性，例如 CPP 与靶向部分的缀合、融合脂质的使用、质子海绵效应的产生等。到目前为止，由于缺乏足够的体内稳定性、免疫测定、毒性和 CPP 的内体逃逸研究，没有任何 CPP 或包含 CPP 的组合物获得食品和药物管理局 (FDA) 的批准。在这篇综述中，我们简要描述了细胞穿透肽的性质、摄取机制、优缺点以及细胞内递药和生物利用度的改善。此外，我们还重点介绍了它们作为有效的药物载体在对抗病毒感染方面的应用。
