Rational design of ferritin nanomaterials for advanced biomedical applications

Ferritin, a ubiquitous iron-storage protein, has emerged as a premier natural nanocarrier in biomedicine, owing to its cage-like architecture, superior biocompatibility, and innate receptor targeting capability. This review comprehensively summarizes the latest advancements in ferritin-based nanoplatforms, focusing on their transformative applications in biomedicine, including the ability to cross physiological barriers for targeted drug delivery to the brain and other organs, the use of ferritin as a modular scaffold for direct disease intervention via domain-specific functionalization, and its role as a potent antigen-presentation platform for next-generation vaccines and immunotherapies. We also examine cutting-edge genetic engineering strategies that are central to enhancing therapeutic efficacy. Key strategies discussed encompass extending plasma half-life, promoting lysosomal escape for efficient intracellular delivery, conferring specialized targeting capabilities, and achieving precise control over ferritin assembly and morphology. By integrating structure-function-application relationships of engineered ferritin, this review provides a roadmap for rational design and highlights its potential to enable novel diagnostic and therapeutic modalities.