Introduction: The low survival rates of late stages of ovarian cancer demonstrate the clear need for more effective therapeutics. Long double-stranded (ds)RNA induces innate immune signalling pathways with anticancer outcomes. dsRNA benefits from a delivery system, as it is lightweight, susceptible to degradation, and negatively charged. A novel nanoparticle derived from sweet corn, nanophytoglycogen (PG), has been developed as a carrier for dsRNA, and the mechanism of the enhanced dsRNA-responses has been explored. PG is a biomaterial that is biodegradable, non-toxic, and non-immunogenic.

Methods/results: PG can carry its own weight in dsRNA, creating “bombs” of concentrated dsRNA – known as GLY-100. In two ovarian cancer cell lines, SKOV-3 and OVCAR-3, we have demonstrated significant GLY-100-induced cell death and/or innate immune induction, measured through cell viability dyes, qPCR, and ELISAs. Compared to dsRNA alone, GLY-100 delivery induced a 45-fold and over 1000-fold increase in CXCL10 transcripts in OVCAR-3 and SKOV-3 respectively. In OVCAR-3, GLY-100 caused robust cell death at concentrations as low as 62.5ng/mL, whereas dsRNA alone did not, even at 500ng/mL. The PG carrier provided protection to the dsRNA from serum nucleases, as assessed in fetal bovine serum protection assays, and enhanced cellular delivery, quantified through fluorescent microscopy. Using expression vectors, we have demonstrated that GLY-100 signals through the type I interferon pathway, as visualized through nuclear translocation of transcription factors IRF3 and STAT1, and movement of the adaptor protein TRIF-1.

Conclusions: These results have demonstrated PG significantly enhances the anticancer potential of dsRNA, and has multiple therapeutic outcomes, the induction of a robust interferon response mediate by type I interferon and dsRNA-mediated cell death. Our findings have led to the initiation of in vivo efficacy testing.