Engineered macrophage nanosponges could keep sepsis in check.

Sepsis, bacteria in blood. 3D illustration showing rod-shaped bacteria in blood with red blood cells and leukocytes

Sepsis is the overreaction of the body’s immune system to infection capable of causing tissue damage, organ failure, and death.  Sepsis-causing bacteria secrete toxic molecules known as endotoxins which trigger immune cells shown to play a major role in inflammation.  These immune cells recognize the endotoxins as dangerous and produce proteins called pro-inflammatory cytokines.  These cytokines activate other macrophages to produce more cytokines, setting off a dangerous condition known as the cytokine storm, causing the immune system to attack the body with catastrophic results. Now, a study from researchers at the University of California San Diego develops macrophage nanosponges capable of safely absorbing and removing molecules from the bloodstream known to trigger sepsis. The team states their macrophage nanosponges, 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 disguising nanoparticles as the body’s own cells. A previous example involves red blood cell nanosponges to combat and prevent MRSA infections where nanoparticles are cloaked with platelet cell membranes to repair wounded blood vessels.  Another example includes nanofibers cloaked in beta cell membranes that could be used to help diabetes patients produce more insulin.  The current study shows 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 by soaking the cells in a solution to make the cells burst, leaving the membranes behind. The membranes were then collected using a centrifuge, mixed with ball-shaped nanoparticles made of a biodegradable polymer, an action that coated the nanosponges with macrophage cell membranes.

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

The team surmises they have developed biomimetic nanoparticles that possess an antigenic exterior identical to macrophage cells, thus inheriting their capability to bind to endotoxins and proinflammatory cytokines. They go on to add 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 the next steps include manufacturing the nanosponges in greater amounts and conducting large animal trials.

Source: University of California San Diego

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