Lv Shixian, Sylvestre Meilyn, Prossnitz Alexander N, Yang Lucy F, Pun Suzie H
Department of Bioengineering, University of Washington, Seattle, Washington 98195, United States.
Chem Rev. 2021 Sep 22;121(18):11653-11698. doi: 10.1021/acs.chemrev.0c00963. Epub 2021 Feb 10.
In recent decades, peptides, which can possess high potency, excellent selectivity, and low toxicity, have emerged as promising therapeutics for cancer applications. Combined with an improved understanding of tumor biology and immuno-oncology, peptides have demonstrated robust antitumor efficacy in preclinical tumor models. However, the translation of peptides with intracellular targets into clinical therapies has been severely hindered by limitations in their intrinsic structure, such as low systemic stability, rapid clearance, and poor membrane permeability, that impede intracellular delivery. In this Review, we summarize recent advances in polymer-mediated intracellular delivery of peptides for cancer therapy, including both therapeutic peptides and peptide antigens. We highlight strategies to engineer polymeric materials to increase peptide delivery efficiency, especially cytosolic delivery, which plays a crucial role in potentiating peptide-based therapies. Finally, we discuss future opportunities for peptides in cancer treatment, with an emphasis on the design of polymer nanocarriers for optimized peptide delivery.
近几十年来，具有高效能、优异选择性和低毒性的肽已成为癌症治疗中颇具前景的治疗药物。随着对肿瘤生物学和免疫肿瘤学理解的加深，肽在临床前肿瘤模型中已显示出强大的抗肿瘤功效。然而，具有细胞内靶点的肽向临床治疗的转化受到其固有结构局限性的严重阻碍，如全身稳定性低、清除快和膜通透性差，这些因素妨碍了细胞内递送。在本综述中，我们总结了聚合物介导的肽用于癌症治疗的细胞内递送的最新进展，包括治疗性肽和肽抗原。我们重点介绍了设计聚合物材料以提高肽递送效率的策略，特别是胞质递送，这在增强基于肽的治疗中起着关键作用。最后，我们讨论了肽在癌症治疗中的未来机遇，重点是设计用于优化肽递送的聚合物纳米载体。
