Coordinating Poly(I:C) and Aluminum within Liposomal Vesicles for Enhanced Innate Immune Activation

Abstract

PolyIC is a double-stranded RNA formed by two complementary ribonucleic acid chains: inosine and cytidine. It is a synthetic analog RNA that mimics the viral genome. PolyIC can activate downstream signal pathways to trigger interferon (IFNs) production after it is uptaken by antigen presenting cells and recognized by the Toll-like receptors (TLRs) located in the endosomal system. The productions of interferon have the functions such as enhancing antigen presentation and immune modulation, and stimulating innate immune responses. However, the delivery of PolyIC into tumors is hampered by RNases present in physiological conditions, which leads to enzymatic degradation. To address the delivery challenge, we encapsulated and stabilized the PolyIC into liposomes, which are lipid-bilayer nanoparticles that enclose and carry drugs inside the core, using the coordination of metals and phosphate on ribose. By using aluminum as the coordination metal, an adjuvant often used with vaccines to enhance immunity, we found that PolyIC synergized with coordinating aluminum to activate macrophages and increase the production of interferons. The results proved that the coordinating liposomes Al-PolyIC allowed for evasion from enzymatic degradation and enhancement of innate immune response.