Lonnie Shea, University of Michigan–Ann Arbor
Intravenous Nanoparticle Delivery for Reprogramming Immune Cells and Modulating Inflammatory Disease
Written by Jessalyn Low Hui Ying
While the immune system plays a critical role for protection against diseases and infections, an undesired immune response can result in many pathological conditions and inflammatory diseases. In this talk, Lonnie Shea presents his research team’s work on using nanoparticle delivery to reprogram immune cells for modulating immune response.
Shea first explained that the main motivation behind this research is autoimmune diseases. In the treatment of autoimmune diseases, establishment of peripheral tolerance, which involves antigens presented by antigen-presenting cells (APCs), is important. Therefore, the researchers developed nanoparticles to deliver antigens, targeting the peripheral tolerance pathway. Here, poly(lactide-coglycolide) (PLG) nanoparticles were encapsulated with antigens, which were then studied using an experimental autoimmune encephalomyelitis model. The researchers discovered that when nanoparticles were delivered with the correct antigen (PLP139–151), immune response was suppressed for over 400 days which prevented the progression of autoimmune disease. Decreased spinal cord inflammation was also observed, consistent with antigen being delivered. Shea highlighted that here, getting an antigen-specific response is key for immune tolerance, rather than broadly suppressing immune response.
Shea next presents the use of these nanoparticles for spinal cord injury (SCI). In SCI, inflammatory monocytes and neutrophils are mobilized from the blood and spleen to the injured spinal cord, which contributes to inflammation and injury. To reprogram these immune cells through physicochemical means, the researchers similarly used PLG nanoparticles, drug-free. Here, the immune cells work to engulf the nanoparticles and are redirected away from the spinal cord to the spleen. Using hemisection SCI models, results following intravenous nanoparticle delivery showed that the immune cells were successfully colocalized with the nanoparticles. Majority of these immune cells were accumulated in the spleen, with only small amounts in the spinal cord, consistent with decreased spinal cord inflammation. Furthermore, the nanoparticles were shown to induce a pro-regenerative, anti-inflammatory phenotype in the immune cells, resulting in axonal regeneration and myelination following SCI. This suggests the capacity for immunomodulation of inflammatory immune cells through nanoparticle delivery to provide a more robust functional recovery.
Shea ends the talk reporting recent work where the researchers use nanoparticles to reduce the metastatic spread of cancer. By targeting the circulating immune cells, the formation of pre-metastatic niches (pMN), which contributes to metastasis, may be prevented. Results showed that nanoparticle treatment combined with anti-PD1 drugs decreased tumor size and metastasis, as well as prolonged survival.