Supramolecular organometallic cages, namely MOCs and MOFs, are highly porous entities constructed by the self-assembly of metal ions and the bridged organic linkers. Their unique structural features, such as permanent porosity, large surface, ease of functionalization, and structural diversity, have attracted worldwide research interest over the past two decades on both structural design and synthesis as well as investigation of potential applications. They have been widely applied to deliver a variety of small-molecule pharmaceuticals over the past two decades, as evidenced by an increasing number of general reviews. Inspired by the successful delivery of small-molecule drugs, their potential capabilities in the binding, protection, and delivery of therapeutic biomacromolecules have attracted research interests in recent years.
Small RNA is an essential macromolecule in all biological cells. Scientists have found that small RNA, including small interference RNA (siRNA) and microRNA (miRNA), have the gene-silencing ability to interfere disease gene expression in a specific and efficient way, which can be utilized for the therapy of the diseases. However, the relevant applications have been severely hampered by their biodegradation, low cellular uptake and target delivery. To overcome these limitations, MOCs and MOFs were employed as host materials for therapeutic RNA stabilization and delivery in this Ph.D. project. Specific non-covalent interactions, such as π stacking, coordination and electrostatic interaction, contribute to the strong RNA binding and stabilization. In addition to protecting bound RNA from enzymatic hydrolysis, both MOCs and MOFs significantly enhanced cellular uptake of RNA and delivered the RNA to the target cancer cell with high efficiency. Interestingly, these proposed MOCs or MOFs-based delivery systems demonstrated the potential synergistic effect of RNA gene regulation and photodynamic therapy of the delivery host and/or chemotherapy of the co-loaded small-molecule drugs. In conclusion, this PhD study presents the design and synthesis of MOCs- and MOFs-based nanostructures for therapeutic RNA stabilization and delivery, providing new insight into the development of MOCs- and MOFs-based sRNA delivery vehicles as well as novel candidates for synergistic tumor therapy