Chemical Engineering Journal, 22 October, 2024, DOI：https://doi.org/10.1016/j.cej.2024.157033

ATP-activated Fe(Ⅲ)/carbon dots assemblies for in situ generating nanozyme and simultaneously monitoring tumor cell ferroptosis

Jian Li, Jian Wang, Ke Liang, Xiaokuang Xue, Tiejin Chen, Zekun Gao, Haohui Ren, Lizeng Gao, Jiechao Ge

Abstract

The integration of nanomedicine and nanocatalysis has currently resulted in the emergence of synthesized nanozymes with disruptive potential in alternative cancer therapy. However, the in situ synthesis of nanozymes using an intracellular components remains a formidable challenge. In this study, the inactivated Fe(Ⅲ)/carbon dots nanoassemblies (Fe/CDs-A) were prepared through Fe³⁺-induced assembly of red emissive CDs. In tumor cells overexpressing adenosine triphosphate (ATP), Fe/CDs-A can be activated and disassembled, causing the specific release of CDs and simultaneous formation of Fe³⁺-ATP nanocomplexes in situ due to the enhanced coordination between intracellular ATP and Fe³⁺. Intriguingly, Fe³⁺-ATP nanocomplexes were found to possess peroxidase (POD)-like activity, efficiently generating highly toxic •OH in the presence of acidic H₂O₂ in tumor cells, thereby inducing tumor cells ferroptosis. Simultaneously, the released CDs initially penetrate the lysosomes of tumor cells and ultimately accumulate in the nuclei of dead/dying cells, achieving real-time monitoring cell death process through their recovered red emission. Overall, for the first time, the well-designed Fe/CDs-A demonstrates its capability as ATP-triggered inducers for in situ generation of nanozymes and specific release of CDs. This study offers a novel pathway for in situ generation of nanozymes for precise cancer therapy.

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