Neutrophil extracellular traps (NETs) facilitate the extracellular killing of pathogens. However, in recent years, excessive NET formation has been implicated in several pathological conditions. Indeed, NETs that are not removed from tissues or from the circulation might serve to trigger autoimmune responses. We observed that physiological amounts of DNase I do not suffice to completely degrade NETs in vitro, suggesting that additional mechanisms are required for the removal of these extracellular structures. We show in this article that human monocyte–derived macrophages are able to engulf NETs in a cytochalasin D–dependent manner, indicating that this is an active, endocytic process. Furthermore, preprocessing of NETs by DNase I facilitated their clearance by macrophages. In addition, both recombinant C1q and endogenous C1q derived from human serum were found to opsonize NETs, and this facilitated NET clearance. Upon internalization, NETs were apparently degraded in lysosomes, as treatment with chloroquine led to accumulation of extranuclear DNA in human monocyte–derived macrophages. Finally, uptake of NETs alone did not induce proinflammatory cytokine secretion, whereas LPS-induced production of IL-1β, IL-6, and TNF-α was promoted by the uptake of NETs. In summary, we show that macrophages are capable of clearance of NETs and that this occurs in an immunologically silent manner.

Murine bone marrow macrophages were able to recognize gold nanoparticle peptide conjugates, while peptides or nanoparticles alone were not recognized. Consequently, in the presence of conjugates, macrophage proliferation was stopped and pro-inflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6, as well as nitric oxide synthase (NOS2) were induced. Furthermore, macrophage activation by gold nanoparticles conjugated to different peptides appeared to be rather independent of peptide length and polarity, but dependent on peptide pattern at the nanoparticle surface. Correspondingly, the biochemical type of response also depended on the type of conjugated peptide and could be correlated with the degree of ordering in the peptide coating. These findings help to illustrate the basic requirements involved in medical nanoparticle conjugate design to either activate the immune system or hide from it in order to reach their targets before being removed by phagocytes.

Single-walled carbon nanotubes (SWCNTs) have become potential candidates for a wide range of medical applications including sensing, imaging, and drug delivery. Their photophysical properties (i.e., the capacity to emit in the near-infrared), excellent photostability, and fluorescence, which is highly sensitive to the local environment, make SWCNTs promising optical probes in biomedicine. In this Perspective, we discuss the existing strategies for and challenges of using carbon nanotubes for medical diagnosis based on intracellular sensing as well as discuss also their biocompatibility and degradability. Finally, we highlight the potential improvements of this nanotechnology and future directions in the field of carbon nanotubes for biomedical applications.