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

Abstract Ideal nanoparticle (NP)-based drug and vaccine delivery vectors should be free of inherent cytotoxic or immunostimulatory properties. Therefore, determining baseline immune responses to nanomaterials is of utmost importance when designing human therapeutics. We characterized the response of human immune cells to hydrogel NPs fabricated using Particle Replication in Non-wetting Templates (PRINT) technology. We found preferential NP uptake by primary CD14 + monocytes, which was significantly reduced upon PEGylation of the NP surface. Multiplex cytokine analysis of NP treated primary human peripheral blood mononuclear cells suggests that PRINT based hydrogel NPs do not evoke significant inflammatory responses nor induce cytotoxicity or complement activation. We furthered these studies using an in vivo humanized mouse model and similarly found preferential NP uptake by human CD14 + monocytes without systemic inflammatory cytokine responses. These studies suggest that PRINT hydrogel particles form a desirable platform for vaccine and drug delivery as they neither induce inflammation nor toxicity. From the Clinical Editor: The authors here fabricated hydrogel nanorods using the PRINT (Particle Replication In Nonwetting Templates) fabrication process. They tested the interaction of human immune cells with these particles and found no immunoreactivity. This finding would suggest that monodisperse PRINT particles of identical shape and size could serve a variety of clinical applications. © 2015 Elsevier Inc. All rights reserved. Statements of funding: Ting: NC TRACS 100K1202, UCRF UNC Internal Grants and NIH U19AI109784DeSimone: NIH 8-VP1-CA174425-04 and NIH U19AI109784Sempowski: NIH UC6-AI058607 and NIH U19AI109784Su: NIH R01AI095097 and AI080432 and NIH U19AI109784Robbins: 1F32A1108159-01 and T-32-CA009156-37Roberts: T-32-GM008719 and T32-AI007273-25. Select studies were performed in the Regional Biocontainment Laboratory at Duke University, which received partial support for construction from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) (grant UC6-AI058607). This work was also supported by NC TRACS 100K1202 (Ting and DeSimone), UCRF UNC Internal Grant (Ting), NMSS Cooperative Center Grant (Ting), NIH 8-VP1-CA174425-04 (DeSimone), NIH UC6-AI058607 (Sempowski), NIH R01AI095097/AI080432 (Su) and NIH U19-AI109784 9 (Ting, DeSimone, Sempowski and Su).