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.

Mode of PEG Coverage on Carbon Nanotubes Affects Binding of Innate Immune Protein C1q.

Surface modification of nanoparticles with poly(ethylene glycol) (PEG) is used in biomedicine to increase the circulation time of the particles after intravenous injection. Here, we study the interaction of PEG-covered carbon nanotubes (CNTs) with the serum complement protein C1q. Besides being the target-recognizing unit of the initiating complex for the classical pathway of complement in our innate immune system, C1q is involved in a range of important physiological processes. We modified the surface of multiwalled CNTs with covalently grafted PEG and physically adsorbed PEG. Transmission electron microscopy revealed the interaction of these PEG-coated CNTs with C1q. We found abundant C1q coverage on the PEG-grafted CNTs but not on the CNTs with adsorbed PEG. We tested the ability of these CNTs to activate the complement system using in vitro complement activation assays. None of the CNTs studied activated the C1q-dependent classical complement pathway. These findings are pertinent to the safe design and novel biomedical applications of PEGylated CNTs.

Impact of the surface charge of polydiacetylene micelles on their interaction with human innate immune protein C1q and the complement system.

Polydiacetylene (pDA) micelles have been demonstrated to be effective drug carriers for cancer therapy in mouse model. However, little is known about their interaction with the human complement system, which constitutes an important part of the innate immune system and can cause severe hypersensitivity reactions. Herein, we investigate the influence of micelle surface charge on the binding of complement protein C1q, the target recognition unit that activates the classical complement pathway and performs a range of other important physiological functions. Besides the classical pathway, we also investigate the surface charge effect on complement activities through the other activation pathways, namely, the MBL-dependent lectin pathway and the alternative pathway. We synthesized three samples of pDA micelles bearing neutral, anionic, and cationic surface charge motifs, respectively. Surface plasmon resonance showed that none of these micelles interacted with C1q. Results from serum complement activation assays indicated that all micelles were inert to complement, except for the anionic pDA micelles, which activated the alternative pathway.