In a recent study, scientists at Northwestern University have developed a new form of chemotherapy that could improve treatment for acute myeloid leukemia (AML). The team redesigned the commonly used chemotherapy drug 5-fluorouracil (5-Fu) into spherical nucleic acids (SNAs), which are nanostructures where the drug is woven directly into DNA strands on tiny spheres.
The researchers tested this new therapy in animal models with AML, a fast-progressing blood cancer. Results showed that the SNA-based drug entered leukemia cells much more efficiently than standard 5-Fu and killed cancer cells up to 20,000 times more effectively. It also reduced cancer progression by a factor of 59 and did not produce detectable side effects in healthy tissues.
Chad A. Mirkin, who led the study, said, “In animal models, we demonstrated that we can stop tumors in their tracks. If this translates to human patients, it’s a really exciting advance. It would mean more effective chemotherapy, better response rates and fewer side effects. That’s always the goal with any sort of cancer treatment.”
Mirkin holds several positions at Northwestern University and is known for his work in chemistry and nanomedicine. He explained that traditional chemotherapy drugs like 5-Fu often fail to reach cancer cells efficiently because they are poorly soluble—less than 1% dissolves in biological fluids—leading to limited absorption by the body and significant side effects such as nausea or fatigue.
“We all know that chemotherapy is often horribly toxic,” Mirkin said. “But a lot of people don’t realize it’s also often poorly soluble, so we have to find ways to transform it into water soluble forms and deliver it effectively.”
The SNAs used in this research were invented by Mirkin at Northwestern University. These structures are recognized by cell receptors called scavenger receptors, especially abundant on myeloid cells involved in AML. The SNAs are naturally absorbed by these cells; once inside, enzymes break down the DNA shell and release the drug molecules directly where needed.
“Most cells have scavenger receptors on their surfaces,” Mirkin said. “But myeloid cells overexpress these receptors, so there are even more of them. If they recognize a molecule, then they will pull it into the cell. Instead of having to force their way into cells, SNAs are naturally taken up by these receptors.”
Animal experiments indicated that this approach nearly eliminated leukemia cells from blood and spleen while leaving healthy tissues unharmed.
“Today’s chemotherapeutics kill everything they encounter,” Mirkin said. “So, they kill the cancer cells but also a lot of healthy cells. Our structural nanomedicine preferentially seeks out the myeloid cells. Instead of overwhelming the whole body with chemotherapy, it delivers a higher, more focused dose exactly where it’s needed.”
The next phase for this research will be testing on larger groups of animals before progressing toward clinical trials in humans if funding is secured.
The study was published on October 29 in ACS Nano and received support from Edgar H. Bachrach and the Bachrach Family Foundation, as well as federal agencies including the National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases.