2026-09-29 理化学研究所,東京科学大学
がん細胞中の一酸化炭素（CO）を原料とした抗がん剤合成の概要図
＜関連情報＞
- https://www.riken.jp/press/2026/20260929_2/index.html
- https://www.nature.com/articles/s41467-026-77616-8
内因性一酸化炭素を利用した癌選択的薬剤合成 Harnessing endogenous carbon monoxide for cancer-selective drug synthesis
TMasayuki Kawai, Tsung-Che Chang, Ambara R. Pradipta & Katsunori Tanaka
Nature Communications Published:17 September 2026
DOI:https://doi.org/10.1038/s41467-026-77616-8
Abstract
Synthetic chemistry within living systems offers a transformative strategy for precision medicine by enabling the targeted generation of therapeutic agents directly at disease sites. Carbon monoxide (CO), an endogenous gasotransmitter upregulated in many cancer phenotypes, represents a unique yet underexploited chemical feedstock for such intracellular synthesis. However, the intrinsically low reactivity of CO necessitates transition-metal mediation, which is typically compromised by rapid deactivation by intracellular thiols such as glutathione (GSH). Here, we present a biocompatible albumin-palladacycle complex (APC) platform that harnesses endogenous CO for two distinct functions: the detection of CO levels and the in situ synthesis of cytotoxic phenanthridinone derivatives—a privileged scaffold found in potent poly(ADP-ribose) polymerase (PARP) and topoisomerase inhibitors. Central to this design is a coumarin anchor that directs the palladium center into the hydrophobic binding pocket of albumin, shielding it from thiol-mediated poisoning while facilitating cellular uptake via endocytosis. We demonstrate that this system effectively detects elevated CO in cancer cells and, in a parallel application, enables the in situ synthesis of pharmacologically active agents. Although the associated cytotoxicity is modest, the approach nonetheless suppresses cancer cell growth. This study considerably advances the proof of concept for “therapeutic in vivo synthetic chemistry,” in which disease-associated metabolites are repurposed as structural building blocks for both diagnostic and therapeutic applications.
