(53i) Molecular Engineering Approaches Toward Platform Immuno-Biomaterials

A recent focus in the biomaterials field is to engineer platform immuno-biomaterials that modulate the host immune response through materials design for application in areas including cancer immunotherapy, autoimmune disorder management, and immune-evasion. Molecular engineering represents one strategy towards the development of these platform immuno-biomaterials. Here, we will describe how molecular engineering approaches can be used to create nanomaterials and soft matter that can reprogram the immune response at the molecular and cellular levels for therapeutic benefit in the body. More specifically, this talk will first highlight how molecular engineering strategies can be used to improve the delivery of nucleic acid therapeutics for the immune-mediated treatment of malignant cancers within the body. Nucleic acids are promising therapeutic agents given their ability to regulate gene expression at the molecular level; however, challenges associated with their delivery including their instability, immunogenicity, and inability to passively transfect cellular membranes limits their clinical potential. We employ molecular engineering strategies to develop non-viral nanoparticles capable of delivering mRNAs in vivo with application towards the treatment of melanomas. The effect that fundamental parameters including nanoparticle size, encapsulation efficiency, zeta potential, and particle morphology impart on mRNA-encoded protein expression within target tissues will also be discussed. Our talk will then transition to focus on molecular engineering strategies towards the development of shear-thinning and injectable soft matter for the recruitment of immune cells to a site of injection within the body. Even though some nanoparticles can traffic to specific immune cells at precise locations within the body, it can also be beneficial to instead recruit specific immune cells to a site of injection using cytokines. Although cytokine injections are simple to implement, their biological effects can be short lived; by contrast, cytokine-impregnated implants can recruit immune cells for sustained periods of time but require surgical methods for in vivo implementation. Here, we develop shear-thinning and injectable cytokine-impregnated soft matter that releases cytokines in a sustained fashion to recruit dendritic cells following a single-needle based injection into the body. The effect that fundamental properties including polymer block size, material composition, and cytokine loading impart on cellular recruitment will also be discussed. In summary, our work will not only aim to highlight the impact that nanomaterials and soft matter development can have on medical application, but also will more broadly aim to highlight the generality of molecular engineering strategies towards the development of platform immuno-biomaterials for medical research.