Metalloprotein-Based Nanomedicines: Design Strategies, Functional Mechanisms, and Biomedical Applications

Metalloprotein-based nanomedicines integrate the multifunctionality of metal centers with the engineerability of proteins to construct advanced nanoplatforms for targeted delivery, diagnostic imaging, and multimodal therapy. In these nanomedicines, metal ions or clusters act as functional cores, enabling imaging contrast enhancement, catalytic reactions, and modulation of pathological microenvironments, while protein frameworks provide structural stability, intrinsic biocompatibility, and programmable bio-interfaces. This review summarizes the design principles of three major metalloprotein-based nanomedicines, including native metalloproteins, engineered metalloproteins, and metal-protein hybrid nanostructures, with a focus on ferritin, transferrin, and heme/cytochrome proteins in the contexts of cancer therapy, imaging diagnostics, antimicrobial, and anti-resistance applications. Through discussion of representative metal- and metalloprotein-based nanomedicine candidates, this review highlights the current challenges and outlines opportunities brought by emerging technologies such as artificial intelligence-guided protein design. Collectively, these advances underscore metal- and metalloprotein-based nanomedicines as multifunctional, tunable, and clinically promising platforms that are poised to become an important pillar of future nanomedicine.