Fe-doped carbon dots: a novel biocompatible nanoplatform for multi-level cancer therapy

Tumor treatment still remains a clinical challenge, requiring the development of biocompatible and efficient anti-tumor nanodrugs. Carbon dots (CDs) has become promising nanomedicines for cancer therapy due to its low cytotoxicity and easy customization. Herein, we introduced a novel type of "green" nanodrug for multi-level cancer therapy utilizing Fe-doped carbon dots (Fe-CDs) derived from iron nutrient supplement. With no requirement for target moieties or external stimuli, the sole intravenous administration of Fe-CDs demonstrated unexpected anti-tumor activity, completely suppressing tumor growth in mice. Continuous administration of Fe-CDs for several weeks showed no toxic effects in vivo, highlighting its exceptional biocompatibility. The as-synthesized Fe-CDs could selectively induce tumor cells apoptosis by BAX/Caspase 9/Caspase 3/PARP signal pathways and activate antitumoral macrophages by inhibiting the IL-10/Arg-1 axis, contributing to its significant tumor immunotherapy effect. Additionally, the epithelial-mesenchymal transition (EMT) process was inhibited under the treatment of Fe-CDs by MAPK/Snail pathways, indicating the capacity of Fe-CDs to inhibit tumor recurrence and metastasis. A three-level tumor treatment strategy from direct killing to activating immunity to inhibiting metastasis was achieved based on "green" Fe-CDs. Our findings reveal the broad clinical potential of Fe-CDs as a novel candidate for anti-tumor nanodrugs and nanoplatform.