Wang Longkun, Chen Hongyuan, Wang Fengshan, Zhang Xinke
Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate-based Medicine, Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.
Department of General Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong University, Jinan, People's Republic of China.
Expert Opin Drug Deliv. 2022 Feb;19(2):147-161. doi: 10.1080/17425247.2022.2039621. Epub 2022 Feb 13.
Paclitaxel is a powerful and effective anti-tumor drug with wide clinical application. However, there are still some limitations, including poor water solubility, low specificity, and susceptibility to drug resistance. The peptide-drug conjugates (PDCs) represent a rising class of therapeutic drugs, which combines small-molecule chemotherapeutic drugs with highly flexible peptides through a cleavable or non-cleavable linker. When this strategy is applied, the therapeutic effects of paclitaxel can be improved.
In this review, we discuss the application of the PDCs strategy in paclitaxel, including two parts: the tumor targeting peptide-paclitaxel conjugates and the cell penetrating peptide-paclitaxel conjugates.
Combining drugs with multifunctional peptides covalently is an effective strategy for delivering paclitaxel to tumors. Depending on different functional peptides, conjugates can increase the water solubility of paclitaxel, tumor permeability of paclitaxel, the accumulation of paclitaxel in tumor tissues, and enhance the antitumor effect of paclitaxel. In addition, due to the change of cell entry mechanism, partial conjugates can restore the therapeutic activity of paclitaxel against resistant tumors. Notably, in order to better translate into the clinical field in the future, more research should be conducted to ensure the safety and effectiveness of peptide-paclitaxel conjugates.
紫杉醇是一种临床应用广泛的强效抗肿瘤药物。然而，它仍存在一些局限性，包括水溶性差、特异性低和易产生耐药性。肽-药物偶联物（PDCs）是一类新兴的治疗药物，它通过可裂解或不可裂解的连接子将小分子化疗药物与高度灵活的肽结合。应用该策略可提高紫杉醇的治疗效果。
在本综述中，我们讨论了PDCs策略在紫杉醇中的应用，包括两个部分：肿瘤靶向肽-紫杉醇偶联物和细胞穿透肽-紫杉醇偶联物。
将药物与多功能肽共价结合是将紫杉醇递送至肿瘤的有效策略。根据不同的功能肽，偶联物可提高紫杉醇的水溶性、紫杉醇的肿瘤渗透性、紫杉醇在肿瘤组织中的蓄积，并增强紫杉醇的抗肿瘤作用。此外，由于细胞进入机制的改变，部分偶联物可恢复紫杉醇对耐药肿瘤的治疗活性。值得注意的是，为了在未来更好地转化到临床领域，应进行更多研究以确保肽-紫杉醇偶联物的安全性和有效性。
