RNA‐Micelles as Self‐Assembling Structures for Efficient Co‐Delivery of Synergistic siRNA and Nucleoside Analogues to Treat CRC Lung Metastasis

SiRNA has been widely studied in cancer gene silencing over the last 25 years. However, few siRNA-based therapeutics have been approved by the FDA. An RNA-micelle platform provides a powerful therapeutic tool through simple one-step, high-yield production that is capable of efficient colorectal cancer lung metastasis treatment, a current lethal condition with a short survival rate post-diagnosis. Here, it is reported that the use of RNA-micelles co-carrying siRNA and nucleoside analogues to completely inhibit lung metastasis of colorectal cancer (CRC). The major advantage of the RNA-micelle is the successful co-delivery of siRNA and chemotherapeutic agent in a single delivery vehicle while specifically targeting CRC cells via incorporation of an oncogenic surface receptor ligand. It was found that RNA-micelles could combine to silence survivin protein expression via siRNA delivery, which in turn increased the efficacy of the delivered chemotherapeutic agent. Both siRNA and high-payload nucleoside-analogues were incorporated onto a single micelle, which remained stable during in vivo circulation, rather than individual RNA nanoparticles, thus generating this advantageous synergistic cancer regression. This platform provides a powerful therapeutic tool to address colorectal cancer lung metastasis, a currently serious, lethal disease that has a very poor prognosis following diagnosis.