An Advanced Multivalent Ligand‐Decorated Microsphere Enrichment System Efficiently Captures Circulating Tumor Cells In Vivo

Abstract Capturing circulating tumor cells (CTCs) in vivo from the bloodstream lessens tumor metastasis and recurrence risks. However, the absence of CTC receptors due to epithelial‐mesenchymal transition (EMT), the limited binding capacity of a single ligand, and the complexity of the blood flow environment significantly reduce the efficiency of CTC capture in vivo. Herein, a multivalent ligand‐decorated microsphere enrichment system (MLMES) is crafted that incorporates a capture column replete with an immunosorbent that precisely recognizes and binds the stably expressed cluster of differentiation 44 (CD44) and glucose transporter protein 1 (GLUT1) receptors present on the exterior of CTCs. As peripheral blood flows through the column, CTCs are efficiently captured, achieving an in vivo capture rate of up to 64.2%, the highest reported to date. Moreover, the MLMES demonstrates excellent biocompatibility, broad‐spectrum tumor cells capture, and storage stability. Importantly, it significantly eliminates a substantial quantity of CTCs from peripheral blood, reducing the risk of metastasis. This breakthrough method has broad clinical application potential in preventing tumor metastasis and recurrence, bringing new possibilities for improving cancer treatment.