SOLID nanoparticles clear inflammatory molecules from the blood through liver lysosomes

In mouse experiments, SOLID nanoparticles removed interleukin-6 from the blood and degraded it in the liver

In an article published on July 9, the authors described a particle that captures an inflammatory signal in plasma and carries it to the liver. In a sepsis model, four of the six mice treated with SOLID survived for seven days after a single injection. All six mice treated with an interleukin-6 antibody died.

Interleukin-6 is a signaling protein that immune cells use to communicate. During sepsis, its concentration can rise and increase inflammation. An interleukin-6 antibody binds the protein and prevents it from interacting with its receptor. The authors instead removed the protein from the blood and degraded it together with its carrier.

LYTAC systems already deliver extracellular proteins to lysosomes, which are cellular compartments containing enzymes. One part of a LYTAC binds the target, while the other binds a cell surface receptor. The receptor then carries the bound complex into the cell.

In SOLID, an antibody on the particle surface selects the target. In cell experiments, particles with a deformation-resistant polymer core were taken up almost completely by the lysosomes of several cell types. In the bloodstream, each particle acquired a protein corona, which is a layer of plasma proteins on its surface. The composition of this layer directed the particles mainly to the liver, where lysosomes degraded both the carrier and its bound molecule. The antibody selects the molecule, while the particle properties and blood proteins direct it to the liver for degradation.

Across four independent samples from the sepsis model, serum interleukin-6 levels after SOLID treatment were 70% lower than after interleukin-6 antibody therapy. Seven days after the particles were administered, four of the six mice remained alive, while all six mice in the antibody group had died.

In a separate model of acute lung injury, the particles captured CpG DNA fragments, which are short sequences that resemble bacterial DNA and activate the innate immune response. Across four independent samples, immune cell infiltration into the lungs was 1.7 times lower than after CpG neutralization.

The authors tested this method in two acute mouse models after a single intravenous injection. Under these conditions, the particles bound the selected inflammatory mediator in the blood, entered liver lysosomes, and delivered the mediator to enzymes for degradation.