A Northwestern University team reports that redesigning the chemotherapy drug 5‑fluorouracil as a spherical nucleic acid markedly increased its cancer‑cell uptake and efficacy in acute myeloid leukemia models, with no observable side effects, according to a study published October 29 in ACS Nano.
Northwestern University scientists re‑engineered 5‑fluorouracil (5‑Fu) into a spherical nucleic acid (SNA) — DNA strands densely arranged around a nanoscale core with the drug built into the strands — and tested it against acute myeloid leukemia (AML) in mice. The work, led by Chad A. Mirkin, was published online October 29 in ACS Nano. (news.northwestern.edu)
In cell and animal studies, the SNA version entered leukemia cells 12.5 times more efficiently than standard 5‑Fu and achieved a 59‑fold improvement in antitumor efficacy in a human AML mouse model, with no observable side effects reported. The PubMed record for the paper describes “up to four orders of magnitude” (i.e., up to 10,000‑fold) enhancement in in‑vitro cell killing versus free 5‑Fu; Northwestern’s news materials state killing was “up to 20,000 times” more effective. Taken together, the peer‑reviewed abstract supports at least a 10,000‑fold in‑vitro gain, while university communications cite a higher figure. (pubmed.ncbi.nlm.nih.gov)
The approach aims to solve a long‑standing limitation of 5‑Fu: poor solubility. Less than 1% dissolves in many biological fluids, which hampers absorption and contributes to toxicity from high dosing, Northwestern notes. By integrating the drug into the SNA’s DNA shell, the construct leverages cell‑surface scavenger receptors that myeloid cells overexpress, enabling preferential uptake by AML cells and sparing healthy tissue in the reported mouse experiments. (news.northwestern.edu)
“In animal models, we demonstrated that we can stop tumors in their tracks,” Mirkin said, adding that the goal is more effective chemotherapy with fewer side effects. The study’s next steps include larger cohorts of small animals, progression to a large‑animal model, and, contingent on funding, eventual human trials. (news.northwestern.edu)
Northwestern frames the work within “structural nanomedicine,” in which a therapy’s architecture is tuned to control how it behaves in the body. The university says seven SNA‑based therapies are already in human clinical trials, underscoring the platform’s translational momentum even as the 5‑Fu SNA remains at the preclinical stage. (news.northwestern.edu)
