(27g) Biomaterial Strategies for Modulation of the Innate Immune System for Disease Amelioration

Immunotherapies, i.e., therapies that target the immune system for disease treatment, have emerged as a potent curative strategy for diseases that emanate from immune dysregulation. While adaptive immunity has been at the center stage of immunotherapy development, innate immunity is the key to activating and defining the quality of adaptive immune responses. As such, purposeful modulation of the innate immune response can unlock the full potential of the adaptive response. In this talk, I will present two research projects that demonstrate targeted modulation of innate immune cells for disease amelioration.

In the first work, I will showcase material strategies for the delivery of an immunostimulatory dsRNA, poly(I:C), to activate pattern recognition receptors (PRRs) in cells to direct pro-inflammatory and type-I interferon responses. Compared to soluble poly(I:C) and polyplexes, the best performing linear polyethyleneimine-based layer-by-layer self-assembled microparticles induced up to twelve-fold stronger activation of its cytosolic receptors without compromising the activation of the endosomal receptor, TLR3. In RAW264.7 macrophages, these microparticles induced up to 5- and 25-fold higher production of the pro-inflammatory cytokine, TNFα, and type-I interferon, IFNβ, respectively, than soluble poly(I:C). Such directed stimulation of innate immune cells can be leveraged to drive anti-cancer immune response as well as enhance the quality of humoral response to immunization.

In the second part, I will show how designer nanoparticles can be leveraged to suppress the immune response in the context of microbial insult and inflammation. The leading cellular drivers of inflammation are neutrophils, the most prevalent leukocytes in the bloodstream, and monocytes, macrophages, and dendritic cells that aid the recruitment of adaptive immune cells by secreting pro-inflammatory cytokines and chemokines. Using functional in vitro assays to monitor changes in cytokine and chemokine secretion profiles and cell surface activation markers, the immunosuppressive activity of nanoparticles decorated with polypeptides, polysaccharides, and synthetic polymers will be discussed in the context of surrogate microbial danger signals.