Cancer‐Selective Intracellular Polymerization via Acrolein‐Driven Cyclodimerization Cascade
Abstract
Abstract The intracellular polymerization of synthetic macromolecules presents a unique method for modifying cell behavior, enabling real‐time imaging, and enhancing therapeutic effectiveness. However, most current strategies rely on external catalysts or non‐physiological triggers, often lacking target‐cell specificity. Here, we report a cancer‐selective intracellular cyclodimerization cascade polymerization driven solely by endogenous acrolein, an oncometabolite overproduced in malignant cells. Acrolein plays dual roles as a polymerization initiator through imine formation and as a structural component of the resulting polymer. We designed a meta ‐phenylene‐bis(2‐aminoethanol) monomer that incorporates an aggregation‐induced emission (AIE)‐active tetraphenylethylene unit. In acrolein‐rich cancer cells, condensation between the aminoethanol groups and acrolein generates imines, which then undergo a spontaneous, catalyst‐free cyclodimerization cascade, yielding eight‐membered 1,5‐diazacyclooctane polymers that embed native acrolein. This polymerization triggers robust AIE fluorescence “turn‐on”, facilitating high‐contrast imaging of malignant cells with minimal background in healthy cells. We demonstrated selective fluorescence in multiple cancer cell lines and applied this platform to freshly resected human breast tumor samples, showing its utility for rapid intraoperative assessment. This strategy establishes a versatile toolkit for precision diagnostics, engineered intracellular materials, and next‐generation therapeutics.
Article Details
Authors (12)
Shinji Kawaguchi
Department of Chemical Science and Engineering School of Materials and Chemical Technology Institute of Science Tokyo 2‐12‐1 Ookayama Meguro Tokyo 152–8552 Japan
Ambara R. Pradipta
Department of Chemical Science and Engineering School of Materials and Chemical Technology Institute of Science Tokyo 2‐12‐1 Ookayama Meguro Tokyo 152–8552 Japan
Tomohiro Kubo
Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Institute of Science Tokyo, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
Akihiro Ishiwata
Cluster for Pioneering Research, RIKEN
Takuma Sekiguchi
Department of Chemical Science and Engineering School of Materials and Chemical Technology Institute of Science Tokyo 2‐12‐1 Ookayama Meguro Tokyo 152–8552 Japan
Hiromasa Yoshioka
Biofunctional Synthetic Chemistry Laboratory RIKEN Pioneering Research Institute 2‐1 Hirosawa Wako Saitama 351‐0198 Japan
Takaaki Hatano
Department of Breast and Endocrine Surgery Graduate School of Medicine The University of Osaka 2‐2‐E10 Yamadaoka Suita Osaka 565–0871 Japan
Koji Morimoto
Department of Health Science Faculty of Human Science Osaka International University 6‐21‐57 Todacho Moriguchi Osaka 570–8555 Japan
Tomonori Tanei
Department of Breast and Endocrine Surgery Graduate School of Medicine The University of Osaka 2‐2‐E10 Yamadaoka Suita Osaka 565–0871 Japan
Kenzo Shimazu
Department of Breast and Endocrine Surgery Graduate School of Medicine The University of Osaka 2‐2‐E10 Yamadaoka Suita Osaka 565–0871 Japan
Kotaro Satoh
Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Institute of Science Tokyo, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
Katsunori Tanaka
Cluster for Pioneering Research, RIKEN