Scientists design stable protein complexes for targeted cancer therapy
Auburn University researchers, in partnership with the University of Basel in Switzerland, have discovered a new way to make cancer-targeting protein complexes more stable, opening the door to better cancer treatments. . The study, led by Dr. Rafael Bernardi of Auburn University’s Department of Physics and Dr. Michael Nash of the Department of Chemistry at the University of Basel, focused on PD-L1, a protein that tumors use to hide from the immune system. .
In many cancers, PD-L1 acts as a “shield”, binding to immune cells and signaling them to ignore the cancer, allowing tumors to grow undetected. Blocking PD-L1 can help the immune system recognize and attack cancer cells more effectively.
In this study, the researchers investigated the interaction between PD-L1 and small proteins called “affibodies”. Affibodies are designed to attach to cancer cells and help deliver anti-cancer drugs directly to the tumor. Combining these two proteins could make it easier to deliver therapy precisely where it is needed, making cancer treatments more effective and reducing side effects on healthy cells.
The study, published in ACS Nano, introduces the concept of “force anisotropy” and demonstrates how the strength of PD-L1 and Affibody pairing changes based on the specific point of attachment. I am doing it. The research team found that by adjusting the attachment points of the PD-L1, they could make the pair up to four times stronger.
“This breakthrough improves the way we attach drugs to proteins such as affibodies, allowing them to be effectively found and bound by cancer cells,” said Dr. Diego Gomez, a postdoctoral fellow at Auburn University. There is a possibility.”
“By adjusting where we attach the Affibodies, we can make them stronger, stay intact longer in the body, and be able to reach cancer cells more effectively,” Dr. Bernardi said. ” he explained.
The research team used both laboratory experiments and computer models to test how well the protein complexes could bind together. They show that with the right adjustments, the complexes not only hold stronger, but also grow more stably under tension, making them ideal for delivering therapy directly to cancer cells. I discovered.
This discovery could lead to more reliable drug delivery systems, allowing researchers to develop cancer treatments that target tumors more precisely and have longer-lasting effects. Dr. Bernardi’s team is now looking at designing even more powerful affibody proteins that can more accurately find and bind to different types of cancer.
Beyond drug delivery, this research could also be useful in cancer surgery, with affibodies carrying dyes that can make cancer cells glow under special light, allowing surgeons to spot and spot tumors. help remove it. Radiation can also be used to directly target cancer cells and kill them over time.
Further information: Byingseon Yang et al, Engineering the Mechanical Stability of a Therapeutic Complex between Affibody and Programmed Death-Ligand 1 by Anchor Point Selection, ACS Nano (2024). DOI: 10.1021/acsnano.4c09220
Provided by Auburn University
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