Structural modification strategies for ferritin nanoparticles and their applications in biomedicine: a narrative...

Ferritin is an iron-storage protein that naturally self-assembles into a hollow spherical particle consisting of 24 identical subunits, and it serves a central role in iron metabolism. Ferritin's favorable drug-loading capacity, biocompatibility, intrinsic targeting ability (e.g., via transferrin receptor 1 (TfR1)), and reversible self-assembly make it a promising nanoplatform for various applications, including drug delivery, targeted imaging, environmental remediation, and nanocatalysis. To overcome the limitations of native ferritin and expand its functional repertoire, researchers have employed strategies such as chemical modification, genetic engineering, and biomimetic mineralization. In particular, chemical modification approaches enable conjugation of targeting ligands, fluorescent probes, or polymer coating onto the ferritin surface, which can prolong the circulation time and improve delivery efficiency. Site-directed mutagenesis and fusion protein strategies enhance its stability and specificity while biomimetic mineralization utilizes the inner cavity of ferritin to synthesize metal nanoparticles and construct multifunctional composites. These advancements significantly broaden the scope of ferritin applications with great potential in precision medicine, treatment of neurodegenerative diseases, and biocatalysis. Yet, challenges remain regarding biosafety, scalable preparation, and clinical translation. Future research needs to focus on optimizing modification strategies to improve the stability and targeting efficiency of nano-delivery systems, and integrate new technologies such as artificial intelligence and synthetic biology to construct efficient, low toxicity and multifunctional nano-delivery systems. This review systematically summarizes the progress on ferritin nanoparticles, focusing on their structural characteristics, the potential of their native properties, and key modification strategies to enhance their functionality. We discuss their diverse biomedical applications, providing theoretical and technical references for related research and promoting the development of precision nanomedicine.