Tang Yongquan, Chen Yan, Zhang Zhe, Tang Bo, Zhou Zongguang, Chen Haining
Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Pharmaceutics. 2021 Dec 8;13(12):2116. doi: 10.3390/pharmaceutics13122116.
Cancer stem cells (CSCs) are characterized by intrinsic self-renewal and tumorigenic properties, and play important roles in tumor initiation, progression, and resistance to diverse forms of anticancer therapy. Accordingly, targeting signaling pathways that are critical for CSC maintenance and biofunctions, including the Wnt, Notch, Hippo, and Hedgehog signaling cascades, remains a promising therapeutic strategy in multiple cancer types. Furthermore, advances in various cancer omics approaches have largely increased our knowledge of the molecular basis of CSCs, and provided numerous novel targets for anticancer therapy. However, the majority of recently identified targets remain 'undruggable' through small-molecule agents, whereas the implications of exogenous RNA interference (RNAi, including siRNA and miRNA) may make it possible to translate our knowledge into therapeutics in a timely manner. With the recent advances of nanomedicine, in vivo delivery of RNAi using elaborate nanoparticles can potently overcome the intrinsic limitations of RNAi alone, as it is rapidly degraded and has unpredictable off-target side effects. Herein, we present an update on the development of RNAi-delivering nanoplatforms in CSC-targeted anticancer therapy and discuss their potential implications in clinical trials.
癌症干细胞（CSCs）具有内在的自我更新和致瘤特性，在肿瘤的起始、进展以及对多种抗癌治疗的耐药性方面发挥着重要作用。因此，针对对CSC维持和生物学功能至关重要的信号通路，包括Wnt、Notch、Hippo和Hedgehog信号级联反应，仍然是多种癌症类型中一种有前景的治疗策略。此外，各种癌症组学方法的进展在很大程度上增加了我们对CSCs分子基础的认识，并为抗癌治疗提供了众多新靶点。然而，最近发现的大多数靶点通过小分子药物仍“难以成药”，而外源性RNA干扰（RNAi，包括siRNA和miRNA）的应用可能使我们能够及时将知识转化为治疗方法。随着纳米医学的最新进展，使用精心设计的纳米颗粒在体内递送RNAi可以有效克服单独使用RNAi的固有局限性，因为RNAi会迅速降解且具有不可预测的脱靶副作用。在此，我们介绍了用于CSC靶向抗癌治疗的RNAi递送纳米平台的发展现状，并讨论了它们在临床试验中的潜在意义。
