Biomedical Polymers Laboratory, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China.
Biomedical Polymers Laboratory, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China; Department of Polymer Chemistry and Biomaterials, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
J Control Release. 2018 Nov 28;290:11-27. doi: 10.1016/j.jconrel.2018.09.029. Epub 2018 Oct 2.
The advancement of tissue and cell-specific drug delivery systems is a key to precision cancer therapy. Peptides, with easy synthesis, low immunogenicity and biological functions closely mimicking or surpassing natural proteins, have been actively engineered and explored to provide nanomedicines with the ability to overcome various extracellular and intracellular delivery barriers ranging from phagocytic clearance in the circulation, low tumor penetration, poor cancer cell selectivity, inferior cell penetration, to endosomal entrapment as well as poor blood brain barrier permeation for brain cancer therapy. Anti-tumor studies with peptide-decorated polymeric nanomedicines are currently in the experimental stage. Most of the reported peptide-directed polymeric nanomedicines do have a rather complex design requiring a multi-step reproducible fabrication process. Moreover, many of the proposed peptide-decorated polymeric nanomedicines are still not able to effectively overcome the drug delivery cascade barriers. Consequently, in order to facilitate clinical translation the complexity of the systems has to be reduced, while maintaining the added functions after the introduction of the different peptides and further progress has to be made in passing the various drug delivery barriers. In this review, we give an overview of the rational design, development and preclinical performance of peptide-decorated polymeric nanomedicines, and further discuss their challenges and future perspectives as a next generation cancer treatment modality.
组织和细胞特异性药物输送系统的进步是精准癌症治疗的关键。肽易于合成、免疫原性低，并且生物功能与天然蛋白非常相似或超越天然蛋白，因此被积极地设计和探索，以提供纳米药物，使其具有克服各种细胞外和细胞内输送障碍的能力，这些障碍包括循环中的吞噬清除、低肿瘤穿透性、对癌细胞的选择性差、细胞穿透性差、内体捕获以及血脑屏障通透性差等，以用于脑癌治疗。目前，使用肽修饰的聚合物纳米药物进行抗肿瘤研究处于实验阶段。大多数报道的肽导向聚合物纳米药物的设计都非常复杂，需要经过多步可重复的制造工艺。此外，许多提出的肽修饰的聚合物纳米药物仍然不能有效地克服药物输送级联障碍。因此，为了促进临床转化，必须降低系统的复杂性，同时在引入不同的肽后保持附加功能，并在通过各种药物输送障碍方面取得进一步进展。在这篇综述中，我们概述了肽修饰的聚合物纳米药物的合理设计、开发和临床前性能，并进一步讨论了它们作为下一代癌症治疗方式的挑战和未来前景。
