Correspondence on "Carbon-Dot-Based Dual-Emission Nanohybrid Produces a Ratiometric Fluorescent Sensor for in Vivo Imaging of Cellular Copper Ions".

The 2012 study by Zhu et al. (DOI: 10.1002/anie.201109089) reporting a hybrid nanosystem composed of carbon and CdSe/ZnS quantum dots functionalized with tris(pyridin-2-ylmethyl)ethane-1,2-diamine (CdSe@C-TPEA) as ratiometric fluorescent sensors for intracellular copper imaging remains highly influential, with 499 citations to date (Web of Science, December 4, 2025). As part of the NanoBubbles replication project, we attempted to reproduce key experimental findings following detailed pre-registered protocols. Despite strict adherence to the reported synthesis procedures, we failed to replicate the central claim of Cu2+-induced fluorescence quenching. Furthermore, our analysis reveals significant data anomalies in the original publication, including spectral overlaps with identical noise patterns inconsistent with independent measurements. These findings raise critical concerns regarding data integrity and reproducibility and cast significant doubt on the reliability of Zhu et al.'s reported results.