Study investigates mechanism of nanomaterial clearance by liver

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Study investigates mechanism of nanomaterial clearance by liver

Clearance in the liver of nanomaterials can affect the development of nanomedicine.

One of the biggest challenges to realizing the potential of targeted therapies is keeping nanomaterials from accumulating in the liver or spleen. The liver and spleen are part of the mononuclear phagocyte system. Its job is to filter toxins from the blood stream. Unfortunately, in doing its job, it is also preventing nanotherapies from reaching their target.

To overcome this obstacle a group of researchers from several institutions in Toronto have conducted organ-level and sub-organ level computational, in vitro, and in vivo studies using quantum dots, gold nanoparticles, and silica nanoparticles to better understand the mononuclear phagocyte system and the mechanism by which nanoparticles are sequestered. They found that blood flow rate, cellular phenotype, and physical position in the liver all play a role in nanoparticle uptake. They suggest that future work ought to involve not only nanoparticle design, but some kind of liver pre-conditioning. Their work appears in Nature Materials.

Nanoparticles can be functionalized in such a way that the particle targets a particular cell type. This holds great promise for cancer and other targeted therapies. However, when nanotherapies are tested in the body, the nanoparticle is cleared from the bloodstream via the mononuclear phagocyte system (MPS). This holds true for all types of nanoparticles.

Tsoi, et al. conducted whole-organ and sub-organ analyses to better understand how the MPS system sequesters nanoparticles. For their experiments, they focused on non-degradable “hard” nanoparticles: quantum dots, gold nanoparticles, and silica nanoparticles.

On the whole organ level, Tsoi, et al. found that quantum dots are first cleared by the cells near the portal triad and that there is a clearance gradient through the liver sinusoid during the first pass. Blood flows into the liver through the portal triad and out through the central vein. This was also observed with gold nanoparticles irrespective of surface functionalization, although protein adsorption seemed to play a role in nanoparticle uptake.

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