School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
Auckland Cancer Society Research Centre, University of Auckland, Auckland, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand.
J Control Release. 2017 Mar 28;250:62-76. doi: 10.1016/j.jconrel.2017.02.006. Epub 2017 Feb 4.
Efficient intracellular trafficking and targeted delivery to the site of action are essential to overcome the current drawbacks of cancer therapeutics. Cell Penetrating Peptides (CPPs) offer the possibility of efficient intracellular trafficking, and, therefore the development of drug delivery systems using CPPs as cargo carriers is an attractive strategy to address the current drawbacks of cancer therapeutics. Additionally, the possibility of incorporating Tumor Targeting Peptides (TTPs) into the delivery system provides the necessary drug targeting effect. Therefore the conjugation of CPPs and/or TTPs with therapeutics provides a potentially efficient method of improving intracellular drug delivery mechanisms. Peptides used as cargo carriers in DDS have been shown to enhance the cellular uptake of drugs and thereby provide an efficient therapeutic benefit over the drug on its own. After providing a brief overview of various drug targeting approaches, this review focusses on peptides as carriers and targeting moieties in drug-peptide covalent conjugates and summarizes the most recent literature examples where CPPs on their own or CPPs together with TTPs have been conjugated to anticancer drugs such as Doxorubicin, Methotrexate, Paclitaxel, Chlorambucil etc. A short section on CPPs used in multicomponent drug delivery systems is also included.
高效的细胞内转运和靶向递送到作用部位对于克服癌症治疗的当前缺陷至关重要。细胞穿透肽 (CPP) 提供了高效细胞内转运的可能性，因此，使用 CPP 作为货物载体开发药物递送系统是解决癌症治疗当前缺陷的一种有吸引力的策略。此外，将肿瘤靶向肽 (TTP) 纳入递药系统的可能性提供了必要的药物靶向效果。因此，CPP 和/或 TTP 与治疗药物的缀合提供了一种提高细胞内药物递送机制的潜在有效方法。已经表明，用作 DDS 中货物载体的肽可增强药物的细胞摄取，从而提供比单独药物更有效的治疗益处。在简要概述了各种药物靶向方法之后，本综述重点介绍了肽作为药物肽共价缀合物中的载体和靶向部分，并总结了最近的文献实例，其中 CPP 单独或 CPP 与 TTP 一起与阿霉素、甲氨蝶呤、紫杉醇、苯丁酸氮芥等抗癌药物缀合。还包括 CPP 在多组分药物递送系统中的应用的简短部分。
