Researchers at the RIKEN Cluster for Pioneering Research (CPR) have created a groundbreaking technology that can modify protein identities within the body. This advancement, shared in Nature Communications on October 2, enabled researchers to direct a protein to mouse tumors and subsequently remove it from the body. This suggests that cancer-fighting drugs could be delivered directly to tumors and then eliminated once their job is done.
The technology also shows promise in developing versatile drugs able to move between organs, carrying out different tasks uniquely at each site.
Proteins circulating in the blood are well-suited for delivering targeted treatments to diseases such as cancer. To prevent damage to unintended tissues, the drugs must attach to the correct cells, which necessitates a complex molecular identification system.
The study, led by Katsunori Tanaka at RIKEN CPR, highlights altering the markers on the surface of albumin, the most prevalent protein in blood, thus changing its binding affinities to tissues in mice.
In earlier research, Tanaka's team explored how various glycans, or identification-marking molecules, affected albumin's ability to target cancer. They discovered that identification pattern "A" could target human colon cancer and then be transported to the bladder for excretion, while pattern "B" directed albumin to the liver and subsequently for intestinal excretion.
The innovation in the new study was developing a method to change albumin’s molecular identity once it reaches its destination in the body, utilizing the chemical click-to-release method.
Initially, the team created albumin-1 by attaching pattern "A" to it. Then, they designed a switching mechanism involving a switcher carrying pattern "B" and a partner attached to albumin-1.
Upon interaction in a dish, the switcher initiated the click-to-release reaction—adding "B" identifiers and detaching many "A" identifiers. The resultant albumin mixture was albumin-2, featuring a combination of identification patterns "A" and "B."
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