Nanogubki against sepsis
A group of researchers from the University of California, San Diego has developed nanocubes that can quickly and safely absorb and remove sepsis-causing molecules from the bloodstream. These "sponges" are nanoparticles hidden on the membranes of macrophages. Their use increased survival in mice with sepsis ("blood poisoning").
The method of masking nanoparticles on cell membranes is a technology developed by the head of the study Liangfang Zhang. His group is developing nanomedical treatments based on the technology of masking nanoparticles for the body's own cells. His previous work was the creation of nanocubes from erythrocytes for the prevention and treatment of infections caused by methicillin–resistant staphylococcus aureus; from platelets - to restore the vascular wall; from beta cells of the pancreas – for the treatment of diabetes mellitus.
In the new study, Zhang's group was developing a treatment for sepsis.
Sepsis is a systemic inflammatory response to the ingestion of infectious agents or their toxins into the blood. Sepsis can be complicated by multiple organ failure, septic shock and lead to death.
Sepsis is usually treated with antibacterial drugs. They eliminate the source of infection, but are unable to stop the body's immune response and reduce inflammation.
Pathogens leading to sepsis produce endotoxins – toxic molecules. Macrophages recognize endotoxins and react to them with increased production of pro-inflammatory cytokines, which in turn activate other macrophages, resulting in a sharp increase in the number of pro-inflammatory cytokines. A generalized inflammatory reaction develops, which is life-threatening for the patient.
In a new study, it was demonstrated that microphage nanocubes neutralize endotoxins and reduce the level of proinflammatory cytokines. Nanocubes work like traps: they bind cytokines and endotoxins to nanoparticles on the membranes of macrophages. The spectrum of infections in which nanocubes can be used is quite wide, since they are able to bind various types of endotoxins. The advantage of macrophage nanocubes is that they are not recognized by immune cells as foreign, since the nanoparticles are hidden on the membranes of macrophages.
Nanocubes adsorb endotoxins from the blood.
The researchers used mouse macrophages to create nanocubes. They were placed in a solution, under the influence of which the cells swelled and collapsed. The membranes of the destroyed macrophages were collected by centrifugation, and then nanoparticles from a biodegradable polymer were added to them. As a result, nanoparticles randomly covered the membranes of macrophages.
The resulting nanocubes were injected into mice infected with a lethal dose of E.coli. Four out of 10 mice in this group survived; in the control group that did not receive a nanocube, all mice died. One dose of nanohub significantly reduced the levels of endotoxins and proinflammatory cytokines in mice. This stopped systemic inflammation, and also reduced the number of bacteria in the blood and spleen.
An in vitro experiment using mouse erythrocytes showed that macrophage nanocubes effectively neutralize endotoxins without damaging erythrocytes (left tube). In the right test tube – red blood cells, to which endotoxins are added, without nanocubes.
Currently, Zhang's group is working together with pharmaceutical companies to develop a drug for widespread use. The next step is to study this drug in a larger animal study.
Article by Soracha Thamphiwatana et al. Macrophage-like nanoparticles concurrently absorbing endotoxins and proinflammatory cytokines for sepsis management is published in the journal PNAS.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru According to the materials of the US San Diego News Center: Macrophage Nanosponges Could Keep Sepsis In Check.