In the labs of Cancer Center at Illinois, Xing Wang and his team have made a counterintuitive discovery: the chirality—or "handedness"—of a DNA nanostructure matters as much as its chemistry when it comes to delivering cancer drugs to their targets. By building left-handed chiral patterns of aptamers on DNA origami tubes, the researchers found they could more than double the cancer-killing efficacy of chemotherapy drugs compared to their right-handed equivalents, a finding that upends conventional wisdom about targeted drug design.
The discovery addresses a fundamental challenge in cancer treatment: how to get drugs to kill cancer cells without poisoning healthy ones. Traditional chemotherapy drugs like Daunorubicin, a widely used agent, wash through the entire body, causing collateral damage to the liver, kidneys, and heart. Wang's approach targets the protein CD117, found on the surface of acute myeloid leukemia cells, creating a geometric "key" that only fits those specific cancer cells.
What makes this breakthrough surprising is how the cells themselves responded differently to left- and right-handed nanostructures made from identical molecular ingredients. Both versions initially attached to the cell surface at nearly identical rates, but the cells later "accepted" and pulled in the left-handed tubes while rejecting and detaching the right-handed ones—a phenomenon Wang's team calls cellular enantioselectivity. The left-handed design triggered CD117 dimerization, a process that efficiently opened the cell membrane and allowed internalization. Once inside, the DNA tube dissolved and released Daunorubicin directly into the cancer cell's nucleus, where it caused DNA damage and cell death.
The research, published in Advanced Materials and conducted with collaborators Tingjie Song and Abhisek Dwivedy, relied on rigorous characterization methods to verify their findings. The team used gel electrophoresis, transmission electron microscopy, and super-resolution fluorescence imaging to confirm the structure and behavior of their DNA tubes at the nanoscale. These tools revealed something that chemical analysis alone could never have shown: that the three-dimensional geometry of a delivery vehicle is as critical as its molecular composition.
The insight mirrors a principle that exists throughout biology. Most essential molecules—proteins, DNA—are chiral, and cells have evolved receptors that are similarly "handed." Just as a left glove fits only a left hand, a left-handed drug only fits a left-handed receptor. Many common medicines exploit this principle; ibuprofen, for instance, is active only in its right-handed form. Yet until now, the field of targeted cancer therapeutics had largely overlooked chirality as a design parameter.
"Our work shows that the geometric pattern is also critical for biological function," Song explained in the research report. "This discovery opens doors to a new generation of 'chiral switches' and delivery vehicles that can be fine-tuned to match the specific 3D architecture of cell surface proteins." That insight signals a broader shift in how researchers might approach drug design—not just asking what molecules to use, but how to arrange them in space to achieve the desired biological effect.
For patients with acute myeloid leukemia and other cancers expressing CD117, the implications are substantial. A more efficient delivery system means lower doses might achieve the same therapeutic effect, reducing side effects while improving outcomes. As Wang's team continues refining chiral delivery vehicles, they're laying groundwork for a new generation of cancer treatments that work smarter, not just harder.