Leukemia is a master of disguise. Its most dangerous agents—the cancer stem cells—are few in number but terrifyingly persistent, capable of evading standard chemotherapy by mimicking healthy cells and hiding deep in the bone marrow. They’re the culprits behind many relapses and the reason leukemia remains so tough to eradicate. But a team led by Xing Wang, a professor of bioengineering and chemistry at the University of Illinois Urbana-Champaign, may have found a way to strike at these cancer roots with precision.

Their solution: DNA aptamers—tiny, single-stranded sequences of DNA that act like heat-seeking missiles. Aptamers have the ability to bind to specific targets with high precision, much like antibodies, but with several key advantages. In this study, which was published recently in Advanced Functional Materials, Wang’s team crafted aptamers that not only locate and bind to leukemia stem cells with high specificity but also carry a chemotherapeutic payload—daunorubicin—right into the cell’s heart.

"This work demonstrates a way to get to the root of leukemia,” said Wang. “Targeted cancer treatments often have problems with toxicity or efficacy. Our aptamers seek out these stem cells specifically and kill them effectively."

What makes the approach even more compelling is the dual mechanism of attack. The aptamer itself is toxic to the leukemia stem cell, delivering a first strike. Then it unloads daunorubicin—a drug that normally can’t enter cells easily—for a second, lethal hit. It’s a potent one-two punch.

Precision That Lowers the Dose—and the Risk

The aptamer's design is built around a concept of double targeting. By selecting two biomarkers frequently found on leukemia stem cells—but rare on healthy cells—the researchers improved specificity and reduced the risk of collateral damage. Most antibody-drug conjugates in cancer therapy target a single marker, which can lead to off-target effects when those markers appear on healthy tissues.

“A big thing we showed in this study is that having two targets is better than one in terms of selectivity,” Wang explained. “There are known antibody-drug conjugates for blood cancers that target one marker, but that marker is also found on a lot of healthy cells... But we used two targets: a combination often found in leukemia cancer cells and leukemia stem cells.”

The researchers put their system to the test in both leukemia cell cultures and in live mouse models. In culture, the aptamer alone reduced cancer cells by 40% in just 72 hours. When loaded with daunorubicin, the same aptamer eradicated cancer cells using just 1/500th of the normal dose. In mice, the aptamer-drug combo proved equally impressive—delivering the same therapeutic effect at just 1/10th of the typical clinical dosage without damaging healthy tissues.

“This was exciting to us,” Wang said. “Because in cancer research, what we see in vitro is not always what we see in the body. Yet we saw excellent survivability and tumor reduction in the mice treated with our aptamer-drug conjugates, at one-tenth of the therapeutic dose, and no off-target effects.”

Toward Aptamers for All Cancers?

Beyond its potential as a new leukemia therapy, the study also opens the door to broader applications. The researchers are already eyeing other cancers where aptamer-drug conjugates could be equally game-changing.

“Every cancer cell has a signature in its surface biomarkers,” said postdoctoral researcher Abhisek Dwivedy, the paper’s first author. “If we can find markers that are present uniquely in cancer cells, we can target other cancer types as well.”

And because aptamers are made of DNA, pairing them with different drugs may be easier and more versatile than working with proteins like antibodies.

“In my experience, it’s much easier to pair a drug with DNA molecules than proteins,” Dwivedy added. “So that opens possibilities for delivering more drugs this way.”

With their study, Wang and his team have not only targeted one of cancer’s most evasive forms—they may have unlocked a platform for treating many more.