Phytoglycogen-dsRNA nanoparticles demonstrate differential cytotoxicity and immunostimulatory potential in two ovarian cancer cell lines

Abstract

Ovarian cancer is a leading cause of cancer mortality in women, and novel treatments with improved efficacy are needed to fight ovarian cancer. Double-stranded (ds) RNA, including the synthetic polyinosinic cytidylic acid (poly (I:C), has shown promise as a cancer therapeutic. Phytoglycogen derived from sweet corn, nanodendrix (NDX) is a carrier for dsRNA. The responsiveness to NDX-delivered poly (I:C), NDX-poly (I:C), was tested in two ovarian cancer cell lines, SKOV-3 and OVCAR-3, previously identified as dsRNA-resistant and dsRNA-sensitive, respectively. NDX bound poly (I:C) at a w/w ratio of 2:1 NDX:poly (I:C) and poly (I:C)-NDX was tested for biological activity through uptake and two therapeutic modes of action, cytotoxicity, and immune stimulation. Immunocytochemistry demonstrated both cells bound to poly (I:C)-NDX. In OVCAR-3, poly (I:C)-NDX caused significant cell death, even at concentrations as low as 62.5 ng/mL; no cell death was observed with poly (I:C) alone at concentrations up to 5 μg/mL in SKOV-3 and 0.5 μg/mL in OVCAR-3. In both cell lines poly (I:C)-NDX stimulated the production of CXCL10 protein and transcripts, an innate immune chemokine, and at significantly higher levels than poly (I:C) alone. Interestingly, in response to poly (I:C)-NDX SKOV-3 produced a more robust immune response and higher levels of capase-3/-7 activation compared to OVCAR-3, despite showing no significant cell death. Poly (I:C)-NDX represents a robust and multifunctional therapy, potentiating poly (I:C) and sensitizing resistant cells. Additionally, the SKOV-3 and OVCAR-3 combination represents a powerful comparative model to help unravel dsRNA-mediated immune responses in ovarian cancer cells.