Engineering metal-ion-doped Prussian blue nanoparticles: from rational synthesis to cancer theranostics

Malignant tumors remain a persistent global challenge in public health, with conventional treatment modalities such as surgery, chemotherapy, and radiotherapy suffering from inherent limitations including high recurrence rates, systemic toxicity, and damage to healthy tissues. The emergence of nanomedicine has brought revolutionary breakthroughs in tumor therapy, among which Prussian blue (PB, Fe₄[Fe(CN)₆]₃) and its derivatives have garnered significant attention due to their unique photothermal conversion properties, catalytic activity, and excellent biocompatibility. However, the therapeutic efficacy of PB is constrained by structural factors such as crystal phase and composition. Metal ion doping (e.g., Cu²⁺, Mn²⁺) can optimize the performance of PB by modulating its electronic structure, not only significantly enhancing its physicochemical properties but also leveraging the biological characteristics of the doped metal ions. This review summarizes recent advances in metal-doped PB nanomaterials for tumor therapy. First, we discuss synthetic strategies for PB doped with different metal ions. Next, we examine the regulatory mechanisms of doping on material properties and their applications in tumor treatment. Finally, we address key scientific challenges, including material stability, in vivo metabolic pathways, and biocompatibility, while proposing future research directions. This work aims to provide both theoretical foundations and technical guidance for developing highly efficient and safe PB-based nanotheranostic agents.