Abstract
Gold nanoparticles (AuNP) have been widely used for drug delivery and have recently been explored for applications in cancer immunotherapy. Although AuNPs are known to accumulate heavily in the spleen, the particle distribution within immune cells has not been thoroughly studied. Here, we characterize the cellular distribution of Cy5 labeled 50 nm AuNPs within the immune populations of the spleen from naïve and tumor bearing mice using flow cytometry. Surprisingly, approximately 30% of the detected AuNPs were taken up by B cells at 24 hours, with about 10% in granulocytes, 18% in dendritic cells, and 8% in T cells. In addition, 3% of the particles were detected within myeloid derived suppressor cells, an immune suppressive population that could be targeted for cancer immunotherapy. Furthermore, we observed that, over time, the particles traveled from the red pulp and marginal zone to the follicles of the spleen. Taking into consideration that the particle cellular distribution did not change at 1, 6 and 24 hours, it is highly suggestive that the immune populations carry the particles and migrate through the spleen instead of the particles migrating through the tissue by cell-cell transfer. Finally, we observed no difference in particle distribution between naïve and tumor bearing mice in the spleen and detected nanoparticles within 0.7% of dendritic cells of the tumor microenvironment. Overall, these results can help inform and influence future AuNP delivery design criteria including future applications for nanoparticle-mediated immunotherapy.