Fluorescence‐Switchable Iron‐Doped Nanodot Assembly as a Robust Redox Dyshomeostasis Amplifier for Noninvasive Treatment of Deep‐Seated Tumors

Abstract Carbon dots (CDs) have been recognized as promising candidates for cancer diagnosis and therapy, owing to their intrinsic fluorescence properties and facile functionalization pathways. However, such tiny‐sized CDs tend to be rapidly excreted by the kidney and/or hepatobiliary system before reaching the tumor site, which may significantly weaken their performance in tumor theranostics. Here, fluorescence switchable iron‐doped carbon dot assemblies (FCDDs) are developed with an average size of ≈120 nm for passive tumor targeting. After lesional enrichment, FCDDs can be dissembled into Fe‐doped CDs (FCDs) with fluorescence switched on, in response to the upregulated glutathione (GSH) in the tumor microenvironment. The ultrasmall FCDs are able to penetrate into the deep region of solid tumors and generate reactive oxygen species (ROS) through the Fenton reaction. Such ROS accumulation and GSH deprivation caused by FCDDs can effectively trigger the irreversible apoptosis and ferroptosis of tumor cells. Meanwhile, the resultant intracellular redox dyshomeostasis induces prominent immunogenic cell death to prevent metastasis. Tumor‐specific fluorescence imaging not only enables cancerous tissue probing but also assists in monitoring the treatment effectiveness. Taken together, this paradigm exemplifies a practical approach to improve the functionality of CDs toward clinical applications and may inspire more facile designs toward upcoming translational medicines.