Researchers find blood vessel endothelial cells stop more nanoparticles than the liver

January 29, 2018, Leiden University

Nanoparticles that transport medicines to a specific part of the human body are usually broken down in the liver prematurely. Jeroen Bussmann from Leiden University has discovered a new method to prevent this from happening. Publication in ACS Nano.

In nanotherapy, particles measuring between a nanometer and a micrometer are used to deliver medicines to specific locations in the body, for example to destroy tumours with far fewer side-effects than traditional chemotherapy. A recurrent problem in developing nanotherapy is that the liver often breaks down the nanoparticles prematurely. Consequently, the particles only rarely reach their intended destination. To date, researchers believed this was the work of clean-up – so-called Kupffer cells – in the liver.

Cells from blood vessel walls

In joint research carried out with the Hubrecht Institute and the University of Basel, Jeroen Bussmann, chemical biologist at Leiden University, discovered that cells in the of the liver () often play a much greater role in this process than previously thought. Proteins on the surface of these cells recognise the nanoparticles and eliminate them. Blocking these proteins means that the endothelial cells will no longer recognize the nanoparticles, which then remain in the for longer. This is crucial if medicines are to be reach their intended targets in the body.

Tracking nanoparticles

Bussmann used zebrafish larvae for his research. "The advantage of using these larvae is that they are transparent, so we can follow the nanoparticles using a microscope in the blood vessels," he explains. Bussmann blocked the endothelial cells by giving the zebrafish larvae a special polymer (a long, interlinked molecule). "When this polymer binds to the proteins on the endothelial cells, they no longer recognise the nanoparticles," he explains.

The other clean-up cells in the liver (Kupffer cells) mainly recognise particles larger than 100 nanometers. The idea was that by using smaller nanoparticles in combination with the special polymer, no cells in the liver would still be able to cause the removal of the nanoparticles. This worked: particles administered in this way remain in the blood stream without being broken down.

Blood vessel cells swallow up nanoparticles

The point in time when Bussmann was certain that the endothelial cells had actually ingested the nanoparticles, was when he administered nanoparticles containing a toxic substance to the fish larvae: this substance only acts within cells and not outside them. So, when only the endothelial cells died, he knew that this was because they had ingested the nanoparticles.

Using the zebrafish larvae, Bussmann also discovered precisely which protein in the endothelial cells binds to the particles, namely Stabilin-2. Removing the gene for Stabilin-2 also resulted in much lower breakdown of the nanoparticles. Bussmann now aims to develop a molecule that binds specifically to Stabilin-2. It will then be possible to inhibit the breakdown function of the cells highly specifically, without the liver losing part of its natural function.

Delivering medicines to cells

Bussmann also wants to explore how exactly the protein binds to the particles and how the endothelial cells subsequently ingest them. "We want to understand every step in the process so that we can ultimately produce that can deliver medicines not only to the but to every type of cell in the body."

The article has been published in ACS Nano.

Explore further: Nanoparticles could allow for faster, better medicine

More information: Frederick Campbell et al. Directing Nanoparticle Biodistribution through Evasion and Exploitation of Stab2-Dependent Nanoparticle Uptake, ACS Nano (2018). DOI: 10.1021/acsnano.7b06995

Related Stories

Nanoparticles may pose threat to liver cells, say scientists

April 4, 2006

Researchers at the University of Edinburgh are to study the effects of nanoparticles on the liver. In a UK first, the scientists will assess whether nanoparticles –already found in pollution from traffic exhaust, but also ...

Making vessels leaky on demand could aid drug delivery

June 8, 2017

The endothelial cells that line blood vessels are packed tightly to keep blood inside and flowing, but scientists at Rice University and their colleagues have discovered it may be possible to selectively open gaps in those ...

Recommended for you

Scientists create atomic scale, 2-D electronic kagome lattice

November 19, 2018

Scientists from the University of Wollongong (UOW), working with colleagues at China's Beihang University, Nankai University, and Institute of Physics at Chinese Academy of Sciences, have successfully created an atomic scale, ...

Solving mazes with single-molecule DNA navigators

November 16, 2018

The field of intelligent nanorobotics is based on the great promise of molecular devices with information processing capabilities. In a new study that supports the trend of DNA-based information carriers, scientists have ...

A way to make batteries almost any shape desired

November 16, 2018

A team of researchers from Korea Advanced Institute of Science and Technology, Harvard University and Korea Research Institute of Chemical Technology has developed a way to make batteries in almost any shape that can be imagined. ...

'Smart skin' simplifies spotting strain in structures

November 15, 2018

Thanks to one peculiar characteristic of carbon nanotubes, engineers will soon be able to measure the accumulated strain in an airplane, a bridge or a pipeline – or just about anything – over the entire surface or down ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.