Scientists create “smart” DNA drug that targets cancer cells with extreme precision

Targeted therapies have already reshaped cancer care by directing drugs straight to tumors, helping reduce damage to healthy cells and easing harsh side effects linked to chemotherapy. One of the most successful strategies involves antibody-drug conjugates (ADCs), which use monoclonal antibodies to carry treatments directly to cancer cells.

However, ADCs still have drawbacks. Their relatively large size can limit how well they penetrate tumors, and they can only carry a limited amount of drug. These challenges have pushed scientists to explore new ways to deliver therapies more effectively.

DNA-Based Drug Delivery Offers New Advantages

To overcome these limitations, the UNIGE team designed a system based on short DNA strands. Because these molecules are much smaller than antibodies, they can move more easily through tumor tissue. They can also be engineered to carry multiple components, increasing their potential effectiveness.

A "Two-Key" System for Precision Drug Activation

The new method relies on several separate DNA strands, each carrying a specific function. Some strands include binders that recognize cancer markers, while another carries a toxic drug.

When two distinct cancer markers are present on a cell, the DNA components attach to them and assemble at that exact location. This triggers a chain reaction that builds up more DNA structures at the site, boosting the amount of drug delivered. The process works much like two-factor authentication on a banking website. Both markers must be detected before activation occurs. If one is missing, the reaction does not begin, and the drug remains inactive.

Lab Results Show High Selectivity and Power

In laboratory experiments, the system successfully identified cancer cells with specific combinations of surface proteins and delivered potent drugs directly to them. Nearby healthy cells were not affected.

The researchers also showed that multiple drugs can be delivered together using this approach. This could be important for preventing or overcoming resistance, a common problem in cancer treatment.

"This could mark an important step forward in the evolution of medicine, with the introduction of a self-operating drug system. Until now, computers and AI have helped us design new drugs. What's new here is that the drug itself can, in a simple way, 'compute' and respond intelligently to biological signals," explains Nicolas Winssinger, full professor in the Department of Organic Chemistry of the School of Chemistry and Biochemistry, Faculty of science, UNIGE, and last author of the study.

Drugs That Act Like "Computers"

The system works using the same kind of basic logic found in computing. Just as computers rely on operations like "and," "or," and "not," this technology applies similar rules at the molecular level. In this case, an "and" logic gate ensures that the drug activates only when both cancer markers are present, making the treatment highly selective.

Toward Programmable "Smart" Medicines

In the future, researchers hope to expand this concept by adding more complex logic functions. This could lead to medicines that behave like programmable systems, capable of making more advanced decisions inside the body.

Such treatments could adapt to each patient's unique biology, improving effectiveness while reducing side effects. Rather than replacing doctors, these systems are designed to enhance precision and control in therapy, opening new possibilities for personalized medicine and reshaping how diseases are treated.

The research was supported by the Swiss National Science Foundation and builds on earlier work from the NCCR Chemical Biology program.