Can nanomedicines be pooped out?

Header reprinted (adapted) with permission from Pixabay.

Title: Elimination Pathways of Nanoparticles
Authors: Wilson Poon, Yi-Nan Zhang, Ben Ouyang, Benjamin R. Kingston, Jamie L. Y. Wu, Stefan Wilhelm, and Warren C. W. Chan
Publication Info: ACS Nano, 2019, Article ASAP DOI: 10.1021/acsnano.9b01383

Tiny, tiny crystals called nanoparticles can deliver a cancer drug right to a tumor – using smaller doses of medicine more effectively, without horrible side effects. But these man-made materials are often not biodegradable. What happens to these novel materials after they’re introduced into the body: do they lodge in tissue forever, like some microplastics, or can they be safely excreted? New research from the University of Toronto aims to understand how nanoparticles are eliminated from the body – and how to make these new medicines safer.

Generally, drugs that are introduced into the body are removed when they’re either metabolized (safely broken down) or excreted (removed as solid or liquid waste). But since nanoparticles are so new, scientists aren’t sure what happens to them in the body. Large, non-biodegradable nanoparticles made out of metal atoms are frequently used to deliver drugs in the body but can’t be metabolized, so they’re particularly mysterious.

However, researchers think there are two primary pathways for nanoparticles to be expelled from the body: renal elimination, where the kidneys process waste and excrete it as urine, and hepatobiliary elimination, where waste is processed by the liver and excretes it through the intestines as solid waste (yes, poop). The first pathway typically works for small nanoparticles, but the second pathway, elimination through the liver, is not as well understood.

To categorize the elimination pathways of nanoparticles in the liver, the researchers studied nanoparticles made out of gold. These gold nanoparticles don’t degrade in the body, so they must be eliminated through one of the two pathways if they’re eliminated at all.. The researchers coated the gold nanoparticles with a fluorescent molecule (one that emits light) so that they could track the movement of the gold nanoparticles through mice. They tested different sizes of nanoparticles (from 4 nm to 200 nm in diameter), hypothesizing that the size of the nanoparticle would help determine how it interacted with the liver.

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Figure 1. Diagram of nanoparticles in the mouse bloodstream being sequestered by liver sinusoidal endothelial cells. Reprinted with permission from Poon et al. ACS Nano Article ASAP
DOI: 10.1021/acsnano.9b01383. Copyright 2019 American Chemical Society.

Only a very small amount of the nanoparticles (about 1%) were actually eliminated from the mice during the two-week study – indicating that 99% of the nanoparticles remained behind in the body in some form. The researchers believe that this is due to several cells in the liver that sequester the nanoparticles, preventing them from being excreted. They hypothesize that larger nanoparticles are too big to pass through the pores of these liver cells. Depleting the number of one kind of these cells in the liver of the mice led to more nanoparticles being excreted (up to 11% of the nanoparticles). Moreover, more of the smaller nanoparticles were eliminated than the larger ones, which were more likely to spread through the bloodstream to other organs in the body.

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Figure 2. Diagram showing the interaction of larger and smaller nanoparticles (red dots) with two different types of liver cells: Kupffer cells, which can bind to the nanopaticles, and liver sinusoidal endothelial cells, which can trap larger nanoparticles in pores. Reprinted with permission from Poon et al. ACS Nano Article ASAP DOI: 10.1021/acsnano.9b01383. Copyright 2019 American Chemical Society.

While nanoparticles offer exciting new avenues of medicine, including targeted drug delivery and efficient imaging and diagnosis in living cells, their safety in humans is still being evaluated. Could nanoparticles end up permanently lodged in human tissue, like microplastics? What are the implications for long-term human health? Research like this offers a start on answering these questions.

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