Recognition protein C1q of innate immunity agglutinates nanodiamonds without activating complement.

Nanodiamonds are promising nanomedicines for diagnostic and therapeutic applications. As nanodiamonds are mainly administered intravenously, it is critical to understand the humoral immune response upon exposure to nanodiamonds. Here, we report the interactions of pristine, oxidized, and PEG-functionalized nanodiamonds with human complement, an important part of our humoral innate immunity. In particular, we report the nanodiamond binding properties of the recognition protein of the classical complement pathway: C1q, which also takes part in many other physiological and pathological processes. Our results show similar trends in the effects of C1q on the three types of nanodiamonds. Complement activation assays using human serum show that the nanodiamonds trigger slight activities via the alternative pathway and no response via the classical pathway. Nevertheless, surface plasmon resonance shows that C1q binds the nanodiamonds and transmission electron microscopy reveals their agglutination. Studies with macrophages further show that C1q attachment affects their phagocytosis and cytokine response. The multifunctional protein C1q bound unmodified, oxidized, and PEG-functionalized nanodiamonds (NDs), causing agglutination. Whereas the three types of NDs induced different macrophage responses due to their different surface structure and chemistry, the effect of C1q binding on phagocytosis and cytokine secretion of the macrophages was similar. Attraction of C1q molecules onto the NDs may affect the many physiological processes involving C1q and may alter the effect of ND in biomedical applications. Unlabelled Image [ABSTRACT FROM AUTHOR]