将药物分子有效送达目标部位是一项具有挑战性的任务。在过去的十年中，药物递送系统（DDS）中的几项创新已经极大地提高了药物分子的治疗效果。在各种DDS中，细胞穿透肽（CPPs）基于DDS由于其安全性、有效性、选择性、特异性和易于合成而引起了显著关注。CPPs正在成为一种有效的和高效的制药纳米载体平台，用于成功管理各种重要的人类健康障碍。目前，几种化疗策略失败是由于多种抗癌药物的低溶解度、生物利用度降低和靶向递送。同样，视力威胁性疾病的治疗药物的研发由于眼部解剖和生理的复杂性而面临着挑战。通过发展以细胞穿透肽（CPP）为基础的肽药物共轭物（PDCs），可克服癌症和眼部疾病管理中的这些治疗挑战。CPPs可用于递送各种类型的载体分子，包括核酸、小分子和多肽/蛋白质代理。在本综述中，我们简要介绍了CPPs和用于开发PDCs的链接策略。此外，还详细讨论了采用基于CPP的PDCs进行癌症和眼部疾病管理的最新研究，突出了它们与传统DDS的重要性。综述的后几个部分重点关注目前临床试验的现状以及基于CPP的PDCs在疫苗开发中的未来影响。要点：•细胞穿透肽（CPPs）可以通过共价和非共价结合递送各种载体大分子。•基于CPP的肽药物共轭物（PDCs）可以克服传统药物递送方法的缺点，如生物相容性、溶解度、稳定性和特异性。•针对癌症和眼部治疗的各种PDCs正在进入临床试验阶段。©2023年作者，独家授权Springer-Verlag GmbH Germany，属于Springer Nature的一部分。

Effective delivery of drug molecules to the target site is a challenging task. In the last decade, several innovations in the drug delivery system (DDS) have tremendously improved the therapeutic efficacy of drug molecules. Among various DDS, cell-penetrating peptides (CPPs) based DDS have gathered notable attention owing to their safety, efficacy, selectivity, specificity, and ease of synthesis. CPPs are emerging as an efficient and effective pharmaceutical nanocarriers-based platforms for successful management of various important human health disorders. Failure of several current chemotherapeutic strategies is attributed to low solubility, reduced bioavailability, and off-target delivery of several anti-cancer drugs. Similarly, development of therapeutics for vision-threatening disorders is challenged by the anatomical as well as physiological complexity of the eye. Such therapeutic challenges in cancer and ocular disease management can be overcome by developing cell-penetrating peptide (CPP) based peptide drug conjugates (PDCs). CPPs can be used to deliver various types of cargo molecules including nucleic acids, small molecules, and peptides/proteinaceous agents. In this review, we have briefly introduced CPPs and the linker strategies employed for the development of PDCs. Furthermore, recent studies employing CPP-based PDCs for cancer and ocular disease management have been discussed in detail highlighting their significance over conventional DDS. Later sections of the review are focused on the current status of clinical trials and future implications of CPP-based PDCs in vaccine development. KEY POINTS: • Cell-penetrating peptides (CPPs) can deliver a variety of cargo macromolecules via covalent and non-covalent conjugation. • CPP-based peptide drug conjugates (PDCs) can overcome drawbacks of conventional drug delivery methods such as biocompatibility, solubility, stability, and specificity. • Various PDCs are in clinical trial phase for cancer and ocular therapeutics.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.