A common chemotherapy drug’s hidden potential for becoming a game-changing weapon in the fight against cancer has been revealed by researchers at Northwestern University.
The “hack” achieved by the Northwestern team greatly enhances the potency of the traditional chemotherapy drug 5-fluorouracil (5-Fu) by as much as 10,000-fold, making the once weakly performing drug into what has now been characterized as “a powerful, targeted cancer killer” that shows no signs of side effects on healthy cells.
The achievement is detailed in a new study, which reveals how scientists developed the new treatment using a nanostructure known as spherical nucleic acid (SNA), allowing the drug to be woven into DNA strands that coat extremely small globular structures.
Tests on small animal models targeted a quickly growing malignant disease known as acute myeloid leukemia (AML), which is one of the more treatment-resistant forms of blood cancer.
When contrasted with traditional chemotherapy drug treatments, the team reports its new SNA-based drug displayed a remarkable ability to penetrate leukemia cells—with up to 12.5 times greater efficiency than common therapies—making the new drug as much as 20,000 times more lethal to leukemia cells.
Overall, the team reports that its new SNA-based drug successfully reduced the progression rate of the disease 59-fold, marking a potential milestone in side-effect-free cancer therapy.
Nanomedicine Advances
At the heart of the Northwestern Team’s achievement is the burgeoning field of structural nanomedicine, which allows researchers to leverage the structure and composition of nanomedicines to “steer” the ways they interact with our bodies.
Several other SNA-based therapies are currently in clinical trials, which could signal a bright future for the treatment of not only cancers, but also a range of other diseases.
Chad A. Mirkin, the George B. Rathmann Professor of Chemistry, Chemical and Biological Engineering, Biomedical Engineering, Materials Science and Engineering, and Medicine at Northwestern, led the recent study.
According to Mirkin, the team’s study confirmed the effectiveness of the new treatment in animal models, adding that if their success carries over to human patients, it will be “a really exciting advance.”
“It would mean more effective chemotherapy, better response rates and fewer side effects,” Mirkin said in a statement. “That’s always the goal with any sort of cancer treatment.”
Overcoming the Solubility Issue
In conventional forms of treatment, 5-Fu can cause several side effects since it attacks not only cancer cells, but also healthy tissue. However, the real problem is not so much the drug itself, but rather how the human body processes it during treatment. Since most drugs must dissolve in the bloodstream to penetrate cells, poorly soluble drugs can experience problems with absorption since they maintain a solid form. This is also why chemotherapy causes so many side effects: it is poorly soluble.
To combat such issues, Mirkin and the team worked to discover a better system for delivering 5-Fu into the human body. Enter SNAs, which are nanostructures that are recognized and “invited” into living cells they encounter. Using SNAs as a carrier, the Northwestern team says they were successfully able to incorporate them directly into DNA strands.
“Instead of having to force their way into cells, SNAs are naturally taken up by these receptors,” Mirkin said in a statement. The result is that the team succeeded in changing how 5-Fu interacted with cancer cells, allowing easy absorption via their SNA “carriers.” Acting very much like the concept of a Trojan Horse, the enzymes, once they entered the cell, could easily disassemble the DNA shell and release the drug, killing the cancer cells from within.
Successful trials involving mice revealed that leukemia cells were successfully destroyed using the novel therapy, while healthy surrounding tissue was left unaffected.
By contrast, current chemotherapies “kill everything they encounter,” Mirkin says. “So, they kill the cancer cells but also a lot of healthy cells.” The new SNA-based therapy, he says, “delivers a higher, more focused dose exactly where it’s needed.”
Going forward, Mirkin and his colleagues hope to conduct further tests involving animal models, before eventually moving on to human clinical trials.
The team’s study, “Chemotherapeutic Spherical Nucleic Acids,” was published in the journal ACS Nano.
Micah Hanks is the Editor-in-Chief and Co-Founder of The Debrief. A longtime reporter on science, defense, and technology with a focus on space and astronomy, he can be reached at micah@thedebrief.org. Follow him on X @MicahHanks, and at micahhanks.com.