University of Ljubljana, Medical Faculty, Institute of Biochemistry and Molecular Genetics, Vrazov trg 2, 1000 Ljubljana, Slovenia.
University of Wolverhampton, School of Pharmacy, Faculty of Science & Engineering, Wulfruna Street, Wolverhampton WV1 1LY, UK.
Adv Drug Deliv Rev. 2022 Jan;180:114044. doi: 10.1016/j.addr.2021.114044. Epub 2021 Nov 10.
Extensive research has been undertaken in the pursuit of anticancer therapeutics. Many anticancer drugs require specificity of delivery to cancer cells, whilst sparing healthy tissue. Cell-penetrating peptides (CPPs), now well established as facilitators of intracellular delivery, have in recent years advanced to incorporate target specificity and thus possess great potential for the targeted delivery of anticancer cargoes. Though none have yet been approved for clinical use, this novel technology has already entered clinical trials. In this review we present CPPs, discuss their classification, mechanisms of cargo internalization and highlight strategies for conjugation to anticancer moieties including their incorporation into therapeutic proteins. As the mainstay of this review, strategies to build specificity into tumor targeting CPP constructs through exploitation of the tumor microenvironment and the use of tumor homing peptides are discussed, whilst acknowledging the extensive contribution made by CPP constructs to target specific protein-protein interactions integral to intracellular signaling pathways associated with tumor cell survival and progression. Finally, antibody/antigen CPP conjugates and their potential roles in cancer immunotherapy and diagnostics are considered. In summary, this review aims to harness the potential of CPP-aided drug delivery for future cancer therapies and diagnostics whilst highlighting some of the most recent achievements in selective delivery of anticancer drugs, including cytostatic drugs, to a range of tumor cells both in vitro and in vivo.
已经进行了广泛的研究来寻找抗癌治疗方法。许多抗癌药物需要特异性地输送到癌细胞，同时保护健康组织。细胞穿透肽（CPP）现在已经被广泛认为是细胞内递药的促进剂，近年来已经发展到具有靶向特异性，因此具有靶向输送抗癌货物的巨大潜力。尽管目前还没有一种 CPP 被批准用于临床使用，但这项新技术已经进入临床试验。在这篇综述中，我们介绍了 CPP，讨论了它们的分类、货物内化的机制，并强调了将 CPP 与抗癌药物偶联的策略，包括将其纳入治疗性蛋白质。作为这篇综述的主要内容，我们讨论了通过利用肿瘤微环境和使用肿瘤归巢肽来构建肿瘤靶向 CPP 构建体的特异性的策略，同时承认 CPP 构建体对靶向特定蛋白-蛋白相互作用的广泛贡献，这些相互作用与与肿瘤细胞存活和进展相关的细胞内信号通路有关。最后，还考虑了抗体/抗原 CPP 缀合物及其在癌症免疫治疗和诊断中的潜在作用。总之，本综述旨在利用 CPP 辅助药物输送的潜力，为未来的癌症治疗和诊断提供新的思路，同时强调了最近在选择性输送抗癌药物（包括细胞抑制剂）方面的一些最新进展，包括在体外和体内对多种肿瘤细胞的输送。
