Herein, we report a hierarchically organized, water-dispersible “nanocage” composed of cellulose nanocrystals (CNCs), magnetically powered by iron oxide (Fe₃O₄) nanoparticles to capture circulating tumor cells (CTCs) from the blood of head and neck cancer (HNC) patients. Capturing CTCs from peripheral blood is extremely challenging due to their low abundance, yet their enumeration is clinically validated in assessing progression-free survival in HNC patients.

By engaging multiple hydroxyl groups along the molecular backbone of CNCs, Fe₃O₄ nanoparticles were coordinated onto the CNC scaffold. This structure was further modified through conjugation with the protein transferrin (Tf) to enable targeted capture of CTCs. Owing to the presence of Fe₃O₄ nanoparticles, the nanocages exhibited magnetic properties, allowing CTCs to be captured under the influence of a magnetic field.

Tf–CNC-based nanocages were evaluated using blood samples from HNC patients and their CTC capturing efficiency was compared with the clinically relevant Oncoviu platform. The results demonstrated that CNC-derived nanocages efficiently isolated CTCs from patient blood, achieving approximately 85% capture efficiency relative to the standard platform.

The capture efficiency was found to vary depending on the concentration of transferrin and Fe₃O₄ nanoparticles immobilized onto the CNC scaffold. We envision that the Tf–CNC platform holds significant potential in liquid biopsy applications for the isolation and enumeration of CTCs, enabling early detection of metastasis in cancer.