Surface Coating of Nanoparticles Reduces Background Inflammatory Activity while Increasing Particle Uptake and Delivery

In the study of host−pathogen interactions, vaccines and drug delivery, particulate delivery system are widely used to mimic pathogen size, pattern recognition receptor agonist presentation, and target cells or organs. However, some of the polymeric systems used in particulate delivery have inherent inflammatory properties that are variable and nonspecific. These properties enhance their adjuvant activity, but confound the analysis of signaling mechanisms. Here, we present a method for particle coating with minimal background immune activation via passivation of the surface with silica-silane. We show herein that a silica-silane shell passivates polymer particles rendering them inert to activation of innate immune cells. The method is broadly applicable and can be used to coat polymeric particles of many different compositions. This method of silica-silane coating also allows conjugation of amine-bearing agonists and provides for controlled variation of agonist loading. Finally, we demonstrate our particles maintain and enhance qualities of known pathogens, making this a potentially general method for improving immune agonist activity.