ScholarWorks@성균관대학교

초록

The efficient removal of circulating tumor cells (CTCs) and tumor-derived exosomes (TDEs) from whole blood represents a promising strategy to curb tumor metastasis and recurrence. However, current methods for eliminating CTCs and TDEs are hampered by limited efficiency and poor generalizability. This is primarily attributed to phenotypic heterogeneity and unstable receptor expression patterns exhibited by tumor cells, making it difficult to capture them effectively using traditional approaches. Here, we present a phenotype-independent bioorthogonal capture system (PIBCS) designed to simultaneously and efficiently eliminate CTCs and TDEs from whole blood. PIBCS leverages a synthetic metabolic oligosaccharide, Ac4ManNTz, which has the remarkable ability to be universally incorporated into wide variety of tumor cells and exosomes, regardless of their phenotype. Through this incorporation, tetrazine fragment is introduced, serving as a specific tag for subsequent capture. To achieve the capture, we employ a capture column functionalized with trans-cyclooctene microspheres. This setup takes advantage of the labeling introduced by Ac4ManNTz through inverse electron-demand Diels-Alder reaction, a specific and rapid bioorthogonal reaction. PIBCS achieves relatively high capture efficiencies (72.4% for CTCs and 67.5% for TDEs) under the tested conditions. Importantly, PIBCS demonstrates not only broad-spectrum efficacy but also favorable hemocompatibility under the tested in vitro conditions, providing a basis for future studies exploring its potential relevance to clinical applications. This work establishes a robust and universal materials-based platform for extracorporeal therapies aimed at suppressing tumor metastasis and recurrence. Its high efficiency, broad applicability, and a favorable preliminary biosafety profile suggest that it may have potential for integration with precision oncology approaches, warranting further investigation in future studies.

키워드