Engineering Peptide-Functionalized Biomimetic Nanointerfaces for Synergetic Capture of Circulating Tumor Cells in an EpCAM-Independent Manner

Broad-spectrum detection and long-term monitoring of circulating tumor cells (CTCs) remain challenging due to the extreme rarity, heterogeneity, and dynamic nature of CTCs. Herein, a dual-affinity nanostructured platform was developed for capturing different subpopulations of CTCs and monitoring CTCs during treatment. Stepwise assembly of fibrous scaffolds, a ligand-exchangeable spacer, and a lysosomal protein transmembrane 4 β (LAPTM4B)-targeting peptide creates biomimetic, stimuli-responsive, and multivalent-binding nanointerfaces, which enable harvest of CTCs directly from whole blood with high yield, purity, and viability. The stable overexpression of the target LAPTM4B protein in CTCs and the enhanced peptide–protein binding facilitate the capture of rare CTCs in patients at an early stage, detection of both epithelial-positive and nonepithelial CTCs, and tracking of therapeutic responses. The reversible release of CTCs allows downstream molecular analysis and identification of specific liver cancer genes. The consistency of the information with clinical diagnosis presents the prospect of this platform for early diagnosis, metastasis prediction, and prognosis assessment.