Unsaturated fatty acids (UFAs), with the distinct advantages of good biocompatibility and innate tumor-targeting effect, have been widely investigated for the rational design of chemotherapy agent-unsaturated fatty acid (CA-UFA) prodrugs in cancer therapy. Among them, several CA-UFA prodrugs have successfully entered clinical trials and are promising prospects for potential clinical applications. In addition, CA-UFA prodrug-based nanoparticulate drug delivery systems (nano-DDS), which integrate the advantages of CA-UFA prodrugs and nano-DDS, have been emerging as versatile nano-carriers for the efficient delivery of chemotherapeutics. In this paper, we review the advanced drug delivery strategies based on UFA conjugates and focus on the recent advances in CA-UFA prodrugs and the emerging CA-UFA prodrug-based nano-DDS. First, we discuss the rational design of CA-UFA prodrugs in response to the multiple obstacles in chemotherapy, with particular emphasis on the latest progress in both preclinical studies and clinical trials. Moreover, the emerging CA-UFA prodrug-based nano-DDS are also addressed. Finally, the prospects and potential challenges of CA-UFA prodrug-based drug delivery strategies in chemotherapy are highlighted.

具有良好的生物相容性和先天性肿瘤靶向作用的独特优势的不饱和脂肪酸（UFA）已被广泛研究用于癌症治疗中化学治疗剂-不饱和脂肪酸（CA-UFA）前药的合理设计。其中，几种CA-UFA前药已成功进入临床试验，并在潜在的临床应用中具有广阔的前景。另外，结合了CA-UFA前药和nano-DDS的优点的基于CA-UFA前药的纳米颗粒药物输送系统（nano-DDS）已经成为用于高效化学治疗的通用纳米载体。在本文中，我们回顾了基于UFA共轭物的先进药物递送策略，并将重点放在CA-UFA前药和新兴的基于CA-UFA前药的纳米DDS方面的最新进展。第一的，我们讨论了针对化学疗法中多重障碍的CA-UFA前药的合理设计，尤其着重于临床前研究和临床试验的最新进展。此外，还解决了新兴的基于CA-UFA前药的纳米DDS。最后，强调了基于CA-UFA前药的药物递送策略在化疗中的前景和潜在挑战。