Engineered macrophage nanosponges could keep sepsis in check.


Clinical evidence has indicated that the systemic spread of endotoxins from sepsis plays a crucial role in the pathogenesis of Gram-negative bacterial sepsis. However, currently there are no effective ways to manage the diverse endotoxins released by different bacterial genus, species, and strain.  Now, a study from researchers at the University of California San Diego develops macrophage nanosponges which can safely absorb and remove molecules from the bloodstream that are known to trigger sepsis. The team state that their macrophage nanosponges, which are nanoparticles cloaked in the cell membranes of macrophages, have so far been shown to improve survival rates in mice with sepsis.  The study is published in the journal PNAS.

Earlier studies from the team developed ‘cell membrane cloaking technology’, a biomimetic technique which disguises nanoparticles as the body’s own cells. Previous examples include red blood cell nanosponges to combat and prevent MRSA infections;  nanoparticles cloaked in platelet cell membranes to repair wounded blood vessels; and nanofibers cloaked in beta cell membranes that could be used to help diabetes patients produce more insulin.  The current study shows that macrophage nanosponges can safely neutralize both hard-to-treat endotoxins and pro-inflammatory cytokines caused by sepsis in the bloodstream.

The current study uses macrophage cells from mice to make the nanosponges; the lab soaked the cells in a solution which made the cells burst, leaving the membranes behind. The membranes were collected using a centrifuge, then mixed with ball-shaped nanoparticles made of biodegradable polymer; the mixing step spontaneously coated the nanoparticles in macrophage cell membranes.

The group administered the macrophage nanosponges to a group of mice infected with a lethal dose of E. coli.  Results show that the treatment kept four out of 10 mice in this group alive, while all mice in the untreated group died. The researchers state that one dose of the macrophage nanosponges significantly reduced the levels of endotoxins and pro-inflammatory cytokines in the treated mice. They conclude that this prevented systemic inflammation and also reduced the bacterial count in the blood and spleen of these mice.

The team surmise they have developed biomimetic nanoparticles which possess an antigenic exterior identical to macrophage cells, thus inheriting their capability to bind to endotoxins and proinflammatory cytokines. They go on to add that this detoxification strategy may provide a first-in-class treatment option for sepsis and ultimately improve the clinical outcome of patients.  For the future, the researchers state that the next steps include manufacturing the nanosponges in large scales and conducting large animal trials.

Source: University of California San Diego

 

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