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.