Fenton metal nanomedicines for imaging-guided combinatorial chemodynamic therapy against cancer

Chemodynamic therapy (CDT) is considered as a promising modality for selective cancer therapy, which is realized via Fenton reaction-mediated decomposition of endogenous H₂O₂ to produce toxic hydroxyl radical (•OH) for tumor ablation. While extensive efforts have been made to develop CDT-based therapeutics, their in vivo efficacy is usually unsatisfactory due to poor catalytic activity limited by tumor microenvironment, such as anti-oxidative systems, insufficient H₂O₂, and mild acidity. To mitigate these issues, we have witnessed a surge in the development of CDT-based combinatorial nanomedicines with complementary or synergistic mechanisms for enhanced tumor therapy. By virtue of their bio-imaging capabilities, Fenton metal nanomedicines (FMNs) are equipped with intrinsic properties of imaging-guided tumor therapies. In this critical review, we summarize recent progress of this field, focusing on FMNs for imaging-guided combinatorial tumor therapy. First, various Fenton metals with inherent catalytic performances and imaging properties, including Fe, Cu and Mn, were introduced to illustrate their possible applications for tumor theranostics. Then, CDT-based combinatorial systems were reviewed by incorporating many other treatment means, including chemotherapy, photodynamic therapy (PDT), sonodynamic therapy (SDT), photothermal therapy (PTT), starvation therapy and immunotherapy. Next, various imaging approaches based on Fenton metals were presented in detail. Finally, challenges are discussed, and future prospects are speculated in the field to pave way for future developments.