Nanomaterials for Combination Therapies and Immunomodulation

Surya Mallapragada, Chemical and Biological Engineering, Iowa State University, Ames, United States

We have designed and synthesized a family of block copolymers that exhibit hierarchical multi-scale self-assembly to form reversible gels and macroscale solids. We have tailored the chemistries of these biomaterials to modulate cellular and immune responses. This talk will highlight two distinct applications of these tailored nanomaterials – one in pancreatic cancer therapy and the other involving nanovaccines for influenza. Pancreatic cancer currently has an extremely poor prognosis, with a 95% mortality rate. We have exploited the cationic character and thermoreversible gelation of these materials to design efficient miRNA delivery vectors for pancreatic cancer therapies. Our paradigm for the design of targeted polymeric miRNA delivery vectors uses intracellular differences between different cell types rather than differences on the cell surfaces to enable targeting. miRNA and gemcitabine co-delivery using these nanomaterials led to inhibition of tumor growth and metastasis in a pancreatic cancer model. We have also altered nanomaterial chemistry to modulate immune responses and develop effective polymeric subunit vaccine adjuvants that show promise for safe and efficacious vaccines for infectious diseases such as influenza. There is a need to develop effective vaccines against H5N1, avian influenza, which has the potential to become the next global pandemic threat. We have shown that combination nanovaccines loaded with protein antigens stimulated dendritic cells and elicited robust neutralizing antibody titers. The combination nanovaccines demonstrated efficacy against a live virus challenge, reducing virus load and maintaining body weight upon infection. These two examples illustrate the ability to tailor nanomaterial chemistries to alter cellular and immune responses for desired prophylactic and therapeutic applications.