2026/03/01 by Wangxing Lin, Jun Cheng, Jingqin Chen +4 · 1 voice
Biochemistry, Genetics and Molecular Biology · Chemistry · Engineering · #Molecular Sensors and Ion Detection #Nanoplatforms for cancer theranostics #Protein Degradation and Inhibitors
paper · doi:10.1002/agt2.70310
openalex publication_date 2026/03/01 · openalex created_date 2026/03/09 · openalex updated_date 2026/05/21
ABSTRACT Therapy‐resistant acute myeloid leukemia (AML) depends on mitochondrial oxidative phosphorylation (OXPHOS) to meet its energy demands, and succinate dehydrogenase assembly factor 1 (SDHAF1) is essential for the proper assembly of Complex II in OXPHOS. Targeted inhibition of SDHAF1, therefore, holds great potential for AML therapy, but potent and selective small‐molecule inhibitors of SDHAF1 remain to be developed. Herein, we develop cationic tripyrrole oligomers that selectively accumulate in mitochondria, specifically bind to SDHAF1, and suppress Complex II activity, thereby eradicating AML cells and reducing leukemic burden without discernible systemic toxicity, concomitant with the normalization of white blood cells and restoration of neutrophil, erythrocyte, and platelet levels. Meanwhile, the twisted molecular geometry of tripyrrole oligomers endows them with aggregation‐induced emission properties, enabling real‐time visualization of the therapeutic process. Therefore, these tripyrrole oligomers provide a mitochondria‐targeted SDHAF1‐directed theranostic platform for eradicating OXPHOS‐dependent cancers.