尽管癌症免疫学的最新进展已导致多种免疫疗法获得批准，但在解决难以治疗的癌症方面却观察到进展甚微。在这种背景下，治疗性寡核苷酸，包括干扰RNA、反义寡核苷酸、适体和脱氧核糖核酸酶，由于与传统化疗药物相比能够调节基因表达和蛋白质功能，且毒性较低，因此在癌症治疗方法中发挥着核心作用。然而，裸露寡核苷酸的系统施用面临着许多细胞外和细胞内的挑战，这些挑战可以通过使用有效的递送系统来克服。因此，病毒和非病毒载体可以提高寡核苷酸稳定性和细胞内摄取，增强肿瘤积累，并增加内体逃逸的可能性，同时最大限度地减少其他不利影响。因此，为了更深入地了解各种寡核苷酸的基本作用机制以及裸寡核苷酸给药带来的挑战，本文全面回顾了寡核苷酸递送系统的最新进展，并概述了已完成和正在进行的癌症临床试验，这些试验可以塑造未来肿瘤治疗。© 2024 作者。

Although recent advancements in cancer immunology have resulted in the approval of numerous immunotherapies, minimal progress has been observed in addressing hard-to-treat cancers. In this context, therapeutic oligonucleotides, including interfering RNAs, antisense oligonucleotides, aptamers, and DNAzymes, have gained a central role in cancer therapeutic approaches due to their capacity to regulate gene expression and protein function with reduced toxicity compared with conventional chemotherapeutics. Nevertheless, systemic administration of naked oligonucleotides faces many extra- and intracellular challenges that can be overcome by using effective delivery systems. Thus, viral and non-viral carriers can improve oligonucleotide stability and intracellular uptake, enhance tumor accumulation, and increase the probability of endosomal escape while minimizing other adverse effects. Therefore, gaining more insight into fundamental mechanisms of actions of various oligonucleotides and the challenges posed by naked oligonucleotide administration, this article provides a comprehensive review of the recent progress on oligonucleotide delivery systems and an overview of completed and ongoing cancer clinical trials that can shape future oncological treatments.© 2024 The Author(s).