Cyclodextrins grafted magnetite (Fe₃O₄) nanocarriers for anticancer therapy

This comprehensive review explores the therapeutic promise of cyclodextrin-grafted magnetite (Fe₃O₄) nanocarriers in anticancer applications, focusing on their design, drug delivery mechanisms, biological stability, and therapeutic performance. Systems integrating cyclodextrins (cds) with Fe₃O₄ nanoparticles (Fe₃O₄-cd-drug) have been developed for delivery of key anticancer agents such as docetaxel, irinotecan, paclitaxel, and doxorubicin across 11 cancer cell types. Results demonstrate up to 60% reduced cancer cell viability when using magnetite nanoparticle (Fe₃O₄-np)-cds-docetaxel/irinotecan/doxorubicin systems compared to the pristine drug. cd grafting enhances nanoparticle hydrophilicity, drug encapsulation, colloidal stability, and biocompatibility, enabling sustained and targeted drug release. Direct grafting of cds onto Fe₃O₄ yields superior cytotoxicity of 93% death of epidermoid carcinoma (A431) cells with Fe₃O₄-np-cds-irinotecan system compared to linker-mediated systems. In the case of Fe₃O₄-np-cds-doxorubicin system tested on human breast cancer cell (MCF-7) cells shows 38% cell death and adding hyperthermia kills 30% of cells. Compared to alternative grafting like polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), metal-organic frameworks (MOFs), or carbon-based materials, cds offer unique advantages including Food and Drug Administration (FDA)-approved biocompatibility, pH-sensitive release, and support for combination therapies. Cluster analysis categorized Fe₃O₄-cd-drug systems based on cytotoxic efficiency and drug concentration, identifying structure-function relationships and highlighting the superiority of systems with multimodal surface engineering. Mechanistic insights reveal endocytosis-mediated uptake, lysosomal-triggered drug release, reactive oxygen species (ROS) generation via Fenton-like reactions, and enhanced cytotoxicity under hyperthermia. Despite these advances, gaps remain in understanding inclusion complex chemistry, biodistribution, and structure-activity relationships. This review highlights the potential of Fe₃O₄-np-cds-drug systems and emphasizes the urgent need for systematic molecular and material-level studies to optimize Fe₃O₄-cd-drug systems for translational cancer therapy.