Researchers have created a groundbreaking technology that adjusts the recognized identity of proteins within the body. This advancement enables the targeting of mouse tumors with specific proteins, which can then be removed from the body afterward. As a result, cancer-fighting medications could be delivered directly to tumors and subsequently expelled from the body after fulfilling their purpose. The technology also opens the door for the development of versatile drugs that have the capability to move between different organs, executing distinct functions at each site.
The RIKEN Cluster for Pioneering Research (CPR) has unveiled innovative technology that modifies the recognized identity of proteins inside the body. This research, featured in Nature Communications on October 2, enabled the targeting of mouse tumors using proteins, which can be effectively eliminated from the body afterwards. This innovation suggests that cancer-killing medications could be specifically directed toward tumors and then safely removed from the body after delivering their treatment. Additionally, the technology may allow for the creation of multifunctional drugs capable of traveling to different organs to perform varied tasks.
Proteins circulate throughout the bloodstream, making them perfect candidates for delivering targeted treatments against illnesses like cancer. To prevent damage to non-targeted tissues, these treatments must attach to the right cells, necessitating a complex molecular identity. The study, led by Katsunori Tanaka at RIKEN CPR, aims to modify the identity markers on albumin, the most prevalent protein in the bloodstream, thus adjusting the tissues it can connect with in mouse bodies.
In previous research, Tanaka’s team explored various identification markers—known as glycans—that were attached to albumin to assess their ability to target cancer. They discovered that identification marker ‘A’ could attach to human colon cancer cells while also being transported to the bladder for urine excretion. Conversely, identification marker ‘B’ prompted albumin to be absorbed by the liver and sent to the intestines for elimination.
The significant breakthrough in the new study involved developing a method to modify albumin’s identity markers after it arrived at its intended destination within the body. To accomplish this, the research team employed a technique called the click-to-release method. They first created albumin-1 by appending identification marker ‘A’. Next, they devised a switching mechanism that carried marker ‘B’ and a partner linked to albumin-1. Upon encountering the partner on albumin-1 in a laboratory setting, the click-to-release reaction occurred—identifiers ‘B’ were activated, while many ‘A’ identifiers were shed. Consequently, the modified albumin was designated albumin-2, showcasing a combination of identification markers ‘A’ and ‘B’.
In their initial proof-of-concept trial within mice, the researchers tagged albumin-1 with a fluorescent marker before injecting it into the mouse’s bloodstream, both with and without the switcher. As anticipated, when albumin-1 was injected alongside the switcher, fluorescence was detected in the intestines, mirroring the results noted after administering albumin-2. When albumin-1 was injected without the switcher, fluorescence was exclusive to the blood, bladder, and urine.
After confirming their ability to modify albumin’s surface identity within the body, the team proceeded to test whether they could direct albumin-1 to a tumor and later eliminate it via the intestines, simulating drug delivery and removal. They injected albumin-1 into mouse colon tumors, using the switcher after a brief 10-minute interval. In both scenarios, albumin was observed attaching to tumor cells. Following the administration of the switcher, albumin altered its identity, and a significant amount relocated from the tumor to the intestines within five hours. Without the switcher, albumin-1 did not reach the intestines.
Thanks to the biocompatible reactions employed by this innovative technology, it holds great promise for transforming treatments across various medical conditions. “Our approach could serve as a drug delivery system to facilitate the elimination of a drug or medical radionuclide from a tumor post-treatment,” Tanaka explains, “thus minimizing prolonged exposure that could result in adverse effects. Alternatively, a singular ‘patrolling’ molecule could be utilized for the simultaneous treatment of several diseases—akin to the technology depicted in the film Fantastic Voyage.
