Leukocyte-Inspired Multiscale Hierarchical Interface for High-Efficiency Capture and Gentle Release of Circulating Tumor Cells

Abstract

Circulating tumor cells (CTCs) are emerging as pivotal biomarkers for early cancer metastasis detection, prognosis assessment, and real-time therapeutic monitoring. However, their extreme rarity and phenotypic heterogeneity pose significant challenges for efficient capture and viable recovery. Inspired by the dynamic recognition and adhesion mechanisms of leukocytes under physiological conditions, we developed a red light-responsive leukocyte-inspired multiscale hierarchical interface (g@SoS-PACF) for the specific capture and noninvasive release of CTCs. The platform features a microsphere-nanosphere-polymer brush architecture that mimics key structures and functions of leukocytes, thereby endowing enabling topography-assisted anchoring, enhanced interfacial complementarity, and antifouling performance. In addition, this hierarchical interface increases the local density and mobility of targeting ligands, significantly improving recognition efficiency across heterogeneous CTC subpopulations. A photoresponsive azobenzene-cyclodextrin host-guest system is embedded to enable red light-triggered, reversible trans-cis isomerization, allowing gentle release of intact CTCs. In vitro studies revealed capture efficiencies above 83% across diverse EpCAM-expressing tumor cells, with release efficiencies exceeding 94% and post-release viability greater than 89%. Importantly, clinical validation using blood samples from 15 cancer patients demonstrated reliable isolation of phenotypically diverse CTCs. This work presents a smart bioinspired system with broad implications for rare cell sorting, liquid biopsy technologies, and next-generation precision oncology.