The Expanding Horizons of Chemodynamic Therapy: From Fenton Chemistry to Radical-Driven Biological Applications

Since the integration of Fenton chemistry into biomedicine, chemodynamic therapy (CDT) has rapidly emerged as a vibrant interdisciplinary research frontier. In recent years, exciting advances in both the fundamental understanding and the attractive applications of CDT have greatly enriched the field, expanding its conceptual boundaries and therapeutic potential. In this review, we first summarize the advances in CDT from a chemical perspective, including strategies to optimize reaction centers at the electronic level and approaches to refine reaction environments through cellular metabolic regulation. We then discuss emerging insights into hydroxyl radical (·OH)-mediated biological mechanisms and effects, including CDT-related cell death pathways, newly identified subcellular therapeutic targets, and the growing applications of CDT in antibacterial therapy, wound healing, and immune activation. Furthermore, we summarize ongoing efforts toward clinical translation and outline key challenges and perspectives from a translational standpoint. More importantly, we propose an expanded conceptual framework for CDT in response to the evolving research landscape and present an outlook on the key scientific questions and promising application directions. We hope this review will benefit the disciplinary research paradigm across chemistry, nanotechnology, and biology, providing valuable inspiration for future research in nanomedicine.