title: Local co-administration of gene-silencing RNA and drugs in cancer therapy: State-of-the art and therapeutic potential.
abstract: 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.
authors.affiliation: 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. Electronic address: larsson.mikael@gmail.com.
authors.forename: Mikael
authors.initials: M
authors.lastname: Larsson
authors.affiliation: Department of Materials Science and Engineering, National Chiao Tung University, 1001 Ta-Hseuh Road, Hsinchu City 300, Taiwan, ROC.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Huang
authors.affiliation: Department of Materials Science and Engineering, National Chiao Tung University, 1001 Ta-Hseuh Road, Hsinchu City 300, Taiwan, ROC.
authors.forename: Dean-Mo
authors.initials: DM
authors.lastname: Liu
authors.affiliation: School of Chemical Engineering, The University of Adelaide, Adelaide, South Australia 5005, Australia.
authors.forename: Dusan
authors.initials: D
authors.lastname: Losic
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D020868:Gene Silencing; D015316:Genetic Therapy; D006801:Humans; D035683:MicroRNAs / Q000627:therapeutic use; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D034741:RNA, Small Interfering
keywords: Combinatory treatment; Drug delivery system; RNA; Synergy; Therapeutic substance; Tumor