Researchers at the University of Chicago’s Pritzker School of Molecular Engineering (PME) have devised a completely new potential treatment for COVID-19: nanoparticles that capture SARS-CoV-2 viruses in the body, then use the the body’s own immune system to destroy it.
These “Nanotraps” attract the virus by mimicking target cells infected with the virus. When the virus binds to the nanotraps, the traps sequester the virus from other cells and target it for destruction by the immune system.
In theory, these nanotraps could also be used on variants of the virus, leading to a potential new way to inhibit the virus in the future. Although the therapy is still in the early stages of testing, researchers are considering that it could be administered via a nasal spray as a treatment for COVID-19.
The results were published on April 19 in the journal Material.
“Since the start of the pandemic, our research team has developed this new way of dealing with COVID-19,” Asst said. Teacher. Jun Huang, whose lab led the research. “We have performed rigorous testing to prove that these nanotraps work, and we are excited about their potential.”
Design the perfect trap
To design the Nanotrap, the research team – led by postdoctoral researcher Min Chen and graduate student Jill Rosenberg – looked at the mechanism used by SARS-CoV-2 to bind to cells: a protein in spike form on its surface that binds to an ACE2 receptor protein in the human cell.
To create a trap that would bind to the virus in the same way, they designed nanoparticles with a high density of ACE2 proteins on their surface. Likewise, they designed other nanoparticles with neutralizing antibodies on their surfaces. (These antibodies are created inside the body when a person is infected and are designed to cling to the coronavirus in various ways).
ACE2 proteins and neutralizing antibodies have been used in treatments for COVID-19, but by attaching them to nanoparticles, researchers have created an even more robust system to trap and eliminate the virus.
Made from FDA-approved polymers and phospholipids, nanoparticles are about 500 nanometers in diameter – much smaller than a cell. This means that the Nanotraps can reach more areas inside the body and trap the virus more effectively.
The researchers tested the safety of the system in a mouse model and found no toxicity. They then tested the Nanotraps against a pseudovirus – a less potent model of a virus that does not replicate – in human lung cells in tissue culture plates and found that they completely block entry into the cells.
Once the pseudovirus bound to the nanoparticle – which in testing took about 10 minutes after injection – the nanoparticles used a molecule that calls the body’s macrophages to engulf and degrade the Nanotrap. Macrophages usually eat nanoparticles in the body, but the Nanotrap molecule speeds up the process. The nanoparticles were removed and degraded within 48 hours.
The researchers also tested the nanoparticles with a pseudovirus in an ex vivo pulmonary perfusion system – a pair of donated lungs that are kept alive with a ventilator – and found that they completely blocked infection in the lungs.
They also collaborated with researchers at the Argonne National Laboratory to test the Nanotraps with a live virus (rather than a pseudovirus) in an in vitro system. They found that their system inhibited the virus 10 times better than neutralizing antibodies or soluble ACE2 alone.
A potential future treatment for COVID-19 and beyond
Then the researchers hope to test the system further, including further testing with a live virus and on the many virus variants.
“This is what is so powerful about this Nanotrap,” said Rosenberg. “It is easily modulated. We can replace different antibodies or proteins or target different immune cells, depending on our needs with new variants.”
Nanotraps can be stored in a standard freezer and could ultimately be delivered via an intranasal spray, which would place them directly into the respiratory system and make them more effective.
The researchers claim that it is also possible to serve as a vaccine by optimizing the Nanotrap formulation, thus creating an ultimate therapeutic system for the virus.
“This is the starting point,” Huang said. “We want to do something to help the world.”
The research involved collaborators from different departments, including chemistry, biology and medicine.
Other authors on the paper include Xiaolei Cai, Andy Chao Hsuan Lee, Jiuyun Shi, Mindy Nguyen, Thirushan Wignakumar, Vikranth Mirle, Arianna Joy Edobor, John Fung, Jessica Scott Donington, Kumaran Shanmugarajah, Yiliang Lin, Eugene Chang, Glennall, Pablo Penaloza-MacMaster, Bozhi Tian and Maria Lucia Madariaga.