Compositional analysis of macrophages following phagocytosis of metal nanoparticles. A. Scanning electron microscopy (SEM)/backscatter/energy-dispersive X-ray spectroscopy (EDS) element analysis of human THP-1 macrophages after phagocytosis of Co, Cr, Ti, or Co/Cr/Ti mixture. In the Co (A1, 1–5), Cr (A2, 1–5), and Ti (A3, 1–5) groups only one type of metal was detected, and in the Co/Cr/Ti combination group (A4, 1–5), all three elements were detected; oxygen (A1–A4, 6) was detected in all groups. B. Quantitative analysis of element composition shown in A. Within the regions of interest, oxygen levels in each group were similar, with the Ti group showing higher levels than the Cr group (p < 0.05). The content of Co (9.48 ± 1.92%), Cr (7.81 ± 2.11%) and Ti (13.62 ± 4.95%) in their corresponding groups were similar (p > 0.05). In the Co/Cr/Ti group, the contents of Co (5.70 ± 0.91%) and Ti (1.82 ± 0.62%) were lower than Co (9.48 ± 1.92%) and Ti (13.62 ± 4.95%), while Cr (21.48 ± 4.75%) was higher than in the Cr group (17.93 ± 1.87%). C. Intracellular distribution of Co, Cr and Ti nanoparticles in a typical macrophage of the Co/Cr/Ti group. D. Phagocytosed particles correspond to high electron density regions by backscattering spectroscopy. E. Point scanning shows as in D that the content of Cr in the endosomes of the Co/Cr/Ti group macrophages was around 4-fold higher than that of Co or Ti (p < 0.001).