Analysis of human innate immune responses to PRINT fabricated nanoparticles with cross validation using a humanized mouse model

Nanoparticle formulations intended for human vaccine and therapeutics need to be tested for their capacity to induce cytotoxicity, inflammation and passive immune cell targeting in primary human immune cells. We employed Particle Replication in Non-wetting Templates (PRINT) technology - which allows for precise fabrication of nanoparticles with specified size, charge and composition - to test whether PRINT fabricated hydrogel 80 × 320 nm rods elicit cytotoxic or inflammatory immune responses from primary human immune cells, humanized mice and human serum. We failed to detect inflammation by primary human peripheral blood mononuclear cells (PBMC) ex vivo or using the translational humanized mouse model, while identifying CD14+ human immune cells as the target of these particles in both systems.238