A deep dive into ferritin nanoparticle advancements: experimental and computational perspectives

Ferritin, a natural iron-storage protein, has emerged as a versatile platform in nanotechnology and biomedicine due to its biocompatible 12 nm nanocage, intrinsic targeting via the transferrin receptor 1, and adaptability for diverse applications. This review integrates recent experimental and computational advances in ferritin-based nanoparticles, Ferritin is used for drug delivery, vaccine delivery, gene therapy, imaging and diagnostics, antioxidant therapy, and anti-inflammatory and neuroprotective therapies. Experimentally, ferritin nanocages achieve high-capacity loading (up to 400 molecules per cage) of therapeutics such as doxorubicin, siRNA, and CRISPR-Cas9 through pH-responsive disassembly, passive diffusion, and engineered self-assembly. Its natural TfR1 affinity enables precise tumor targeting and blood-brain barrier penetration, improving outcomes in cancers, infectious diseases, and neurological disorders. Computationally, molecular dynamics simulations predict stable antigen-ferritin interfaces. Density functional theory elucidates metal-oxide interactions in catalytic nanozymes. Machine learning classifiers leverage ferritin biomarkers for iron deficiency anemia detection, and bioinformatics tools like weighted gene co-expression network analysis and protein-protein interaction networks reveal ferritinophagy mechanisms in neurodegeneration and cancer. Docking-guided designs enhance vaccine epitope exposure and PROTAC degradation efficiency, fostering precision diagnostics and sustainable nanocarrier optimization. Despite promising preclinical results, challenges in scalability, long-term immunogenicity, and regulatory validation persist. This review highlights ferritin's revolutionary potential in nanomedicine, proposing future directions for AI-assisted design, personalized therapies, and sustainable nanotechnology to overcome barriers for clinical use.