Impact of the surface functionalization for nanodiamonds biocompatibility: A comprehensive view on ex vivo human blood immune cell types

Abstract Nanodiamonds (NDs) represent a class of carbon nanostructures widely investigated as promising biomedical nanotools. The possible immune system reactions indicate success or failure for any nanosystem bioapplication. Moreover the assessment of the role of nanomaterial functionalization on the immune system response needs to be fully elucidated. We aimed to dissect the immunologic impact of two NDs differing for their functionalization, carboxylic acid modified NDs (NDs-COOH) and amino-functionalized NDs (NDs-NH2), presenting a glycolic chain as spacer. We used human peripheral blood mononuclear cells (PBMCs) as model for potential biomedical scenario of ND interaction with the human body. The NDs immunologic effects were depicted toward the complex mix of PBMCs. The results showed that both functionalizations possess high hemocompatibility but NDs-COOH induced a cell viability reduction, affecting monocytes. The NDs impact was depicted through immune activation markers, immune-response gene expression and cytokine secretion analysis. Immune markers confirmed the impact on monocytes, more evident for NDs-COOH. Both NDs affected the immune response, however NDs-COOH showed more prominent responses, evoking pronounced regulation of immune-modulatory transcripts. The cytokine analysis confirmed gene expression data for proinflammatory cytokines related to the innate response. Our findings reveal that NDs decoration with an amino-terminating chain enhances their immunologic compatibility.