Scientists Test “Smart” Red Blood Cells

The “smart” red blood cells deliver antibiotics that target specific bacteria.

A natural delivery system that uses red blood cells as a vehicle to transport powerful antibiotics throughout the body safely has been developed by physicists at McMaster University. This method allows for the targeting and killing of specific bacteria.

According to the scientists, the platform, which is presented in a recent study published in the journal ACS Infectious Diseases, might help in tackling the ongoing crisis of antibiotic resistance. They modified and tested red blood cells as a carrier for one of the world’s few remaining resistance-proof antibiotics, Polymyxin B (PmB), which is typically regarded as a last-resort treatment owing to its toxicity and devastating side effects, which include kidney damage.

It is used to combat bacteria that are particularly harmful and often drug-resistant, such as E. coli, which may cause a number of severe illnesses including pneumonia, gastroenteritis, and bloodstream infections.

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Researchers have devised a method for opening red blood cells and removing the inner components, leaving just a membrane known as a liposome that can be loaded with drug molecules and put back into the body.

From left to right: Thode postdoctoral fellow Sebastian Himbert, based in the Department of Physics & Astronomy, Michal Feigis, an undergrad student also in the Department of Physics & Astronomy, Hannah Krivic, a graduate student of biophysics at McMaster and lead author of the study and team supervisor Maikel Rheinstädter, a professor in the Department of Physics & Astronomy. Credit: Georgia Kirkos, McMaster University

The process also involves coating the outside of the membrane with antibodies, allowing it to stick to bacteria and deliver the antibody safely.

“Essentially, we are using red blood cells to conceal this antibiotic within so it can no longer interact or harm healthy cells as it passes through the body,” explains Hannah Krivic, a graduate student of biophysics at McMaster and lead author of the study. She conducted the work with undergraduate students Ruthie Sun and Michal Feigis, and Thode postdoctoral fellow Sebastian Himbert, all based in the Department of Physics & Astronomy.

“We designed these red blood cells so they could only target bacteria we want them to target,” says Krivic.

The team, supervised by Maikel Rheinstädter, a professor in the Department of Physics & Astronomy, had also focused on red blood cells in previous work (hyperlink) because they are stable, sturdy, and have a naturally long lifespan, approximately 120 days, giving them ample time to reach different target sites.

“With many traditional drug therapies there are challenges. They tend to degrade rapidly when they enter our circulation system and are randomly distributed throughout our bodies,” Rheinstädter explains. “We often have to take higher doses or repeated doses, which increases exposure to the drug and heightens the risk of side effects.”

Scientists are working on additional applications of the technology, including its potential as a platform to deliver drugs across the blood-brain barrier and directly to the brain, helping patients who suffer from Alzheimer’s or depression, for example, to receive treatment much more quickly and directly.

Reference: “Erythro-PmBs: A Selective Polymyxin B Delivery System Using Antibody-Conjugated Hybrid Erythrocyte Liposomes” by Hannah Krivić, Sebastian Himbert, Ruthie Sun, Michal Feigis and Maikel C. Rheinstädter, 29 September 2022, ACS Infectious Diseases.
DOI: 10.1021/acsinfecdis.2c00017

The study was funded by the Natural Sciences and Engineering Research Council of Canada and the Canada Foundation for Innovation.