2025-10-29 ノースウェスタン大学
<関連情報>
- https://news.northwestern.edu/stories/2025/10/new-nanomedicine-wipes-out-leukemia-in-animal-study
- https://pubs.acs.org/doi/10.1021/acsnano.5c16609
化学療法用球状核酸 Chemotherapeutic Spherical Nucleic Acids
Taokun Luo,Young Jun Kim,Zhenyu Han,Jeongmin Hwang,Sneha Kumari,Vinzenz Mayer,Alex Cushing,Roger A. Romero,and Chad A. Mirkin
ACS Nano Published: October 29, 2025
DOI:https://doi.org/10.1021/acsnano.5c16609
Abstract
Herein, we describe experiments showing that liposomal spherical nucleic acid (SNA) constructs comprised of 5-fluorouracil (5-Fu) are selectively taken up by myeloid cells, including acute myeloid leukemia (AML) cells, and act as chemotherapeutics. Specifically, SNAs with biocompatible phospholipid-based liposome cores and oligonucleotides consisting of 10 units of the chemically interconnected 5-fluoro-2′-deoxyuridine, were designed and synthesized. These oligonucleotides are modified in the 3′ position with hexaethylene glycol and cholesterol end groups, which allow them to be anchored to the liposomal cores. Small-molecule drugs like 5-Fu are conventionally delivered via encapsulation in the liposome interior, but restructuring them in the form of an SNA increases their cellular uptake by up to 12.5-fold and enables preferential delivery to AML cell lines. Up to 4 orders of magnitude enhancement in cell killing was observed using chemotherapeutic SNAs compared to the free small molecule 5-Fu in vitro. In a human AML model based on immunodeficient mice, the chemotherapeutic SNA exhibited 59-fold better antitumor efficacy than 5-Fu and improved AML-associated hematological markers without observable side effects. This study highlights the advantages in potency that can be realized when chemotherapeutics are integrated within SNAs, and it underscores how the structure of nanomedicine can profoundly impact both chemotherapeutic delivery and cell targeting.
