School of Energy and Resources, University College London, 220 Victoria Square, Adelaide, South Australia 5000, Australia; Future Industries Institute, University of South Australia, Mawson Lakes, South Australia 5095, Australia.
Department of Materials Science and Engineering, National Chiao Tung University, 1001 Ta-Hseuh Road, Hsinchu City 300, Taiwan, ROC.
Cancer Treat Rev. 2017 Apr;55:128-135. doi: 10.1016/j.ctrv.2017.03.004. Epub 2017 Mar 16.
Gene-silencing miRNA and siRNA are emerging as attractive therapeutics with potential to suppress any genes, which could be especially useful in combination cancer therapy to overcome multidrug resistant (MDR) cancer. Nanomedicine aims to advance cancer treatment through functional nanocarriers that delivers one or more therapeutics to cancer tissue and cells with minimal off-target effects and suitable release kinetics and dosages. Although much effort has gone into developing circulating nanocarriers with targeting functionality for systemic administration, another alternative and straightforward approach is to utilize formulations to be administered directly to the site of action, such as pulmonary and intratumoral delivery. The combination of gene-silencing RNA with drugs in nanocarriers for localized delivery is emerging with promising results. In this review, the current progress and strategies for local co-administration of RNA and drug for synergistic effects and future potential in cancer treatment are presented and discussed. Key advances in RNA-drug anticancer synergy and localized delivery systems were combined with a review of the available literature on local co-administration of RNA and drug for cancer treatment. It is concluded that advanced delivery systems for local administration of gene-silencing RNA and drug hold potential in treatment of cancer, depending on indication. In particular, there are promising developments using pulmonary delivery and intratumoral delivery in murine models, but further research should be conducted on other local administration strategies, designs that achieve effective intracellular delivery and maximize synergy and feasibility for clinical use.
基因沉默 miRNA 和 siRNA 作为有吸引力的治疗方法正在出现，具有抑制任何基因的潜力，这在联合癌症治疗中尤其有用，可以克服多药耐药 (MDR) 癌症。纳米医学旨在通过功能性纳米载体来推进癌症治疗，该载体将一种或多种治疗剂递送到癌症组织和细胞中，具有最小的脱靶效应、合适的释放动力学和剂量。尽管已经投入大量精力开发具有系统给药靶向功能的循环纳米载体，但另一种简单的替代方法是利用制剂直接施用于作用部位，例如肺部和肿瘤内给药。将基因沉默 RNA 与纳米载体中的药物联合用于局部递药的方法正在出现，并取得了有希望的结果。在这篇综述中，介绍并讨论了将 RNA 和药物联合用于局部递药以产生协同作用的当前进展和策略，以及在癌症治疗中的未来潜力。RNA-药物抗癌协同作用和局部递药系统的关键进展与关于 RNA 和药物局部联合用于癌症治疗的现有文献综述相结合。结论是，取决于适应症，用于局部给予基因沉默 RNA 和药物的先进递药系统在癌症治疗中有一定的潜力。特别是，在小鼠模型中使用肺部和肿瘤内递药有很好的发展前景，但应进一步研究其他局部给药策略、实现有效细胞内递药并最大化协同作用和临床应用可行性的设计。
