Genetically Engineered Cell Membrane‐Coated Magnetic Nanoparticles for High‐Performance Isolation of Circulating Tumor Cells

Abstract Circulating tumor cells (CTCs) are a crucial biomarker for early cancer diagnosis and progress of cancer metastasis. However, the extremely rare CTCs with large amounts of background leukocytes seriously restricte the purity of enriched CTCs. Herein, genetically engineered cell membrane‐coated magnetic nanoparticles with following properties are constructed: I) The leukocyte membrane camouflaged nanoparticles, which could significantly reduce nonspecific binding of homologous leukocytes and achieve high‐purity isolation of CTCs, are prepared by simple one‐step extrusion and II) the cellular membrane stably expressing single‐chain variable fragment (scFv) of anti‐epidermal growth factor receptor (EGFR) antibody could ensure the recognition of EGFR‐positive CTCs. The binding affinity of the resulting nanoparticles toward extracellular EGFR protein improved more than 100‐fold compared with natural cell membrane‐coated nanoparticles. Furthermore, compared with commercial immunomagnetic nanoparticles, the functional nanoparticles achieved a greater capture efficiency in artificial blood samples and the cell purity increased from 64.8% to 93.5%. Consequently, the authors successfully isolate high pure CTCs from 6 out of 6 cancer patients using engineered cell membrane‐coated nanoparticles. This platform exhibits a promising potential for CTC detection in clinical samples, offering an innovative method for cancer diagnosis and prognosis evaluation.