Dual Aptamers Functionalized Biomimetic Magnetic Nanomaterials for High-Efficient Capture of Circulating Tumor Cells

Circulating tumor cells (CTCs) are closely related to the early diagnosis, metastasis, and prognosis of cancer. Their efficient capture and precise analysis are significant for advancing precision medicine in cancer treatment. However, CTCs are extremely rare in the bloodstream, and their phenotypes change during the epithelial-mesenchymal transition (EMT), posing significant challenges for effective capture of CTCs. Current methods, which commonly rely on single antibodies or aptamers targeting the epithelial cell adhesion molecule (EpCAM), cannot avoid false negatives due to phenotypic changes. Moreover, traditional "hard interface" nanomaterials are prone to damaging CTCs, affecting subsequent metabolomics analysis. To address these issues, this study proposes dual-aptamer functionalized cell membrane biomimetic magnetic nanoparticles (CCM-IMBs) to efficiently capture CTCs. CCM-IMBs inherit the "homologous targeting" and gentle "soft interface" characteristics of cell membranes and introduce dual aptamers targeting both the epithelial marker EpCAM and the mesenchymal marker CDH2. Experimental results demonstrate that CCM-IMBs exhibit excellent capture efficiency and specificity for target cells, effectively reducing false negatives caused by phenotypic heterogeneity. Furthermore, CCM-IMBs successfully captured CTCs from the peripheral blood samples of four cancer patients with different types of tumors. Additionally, single-cell metabolomics analysis validated that the capture process using CCM-IMBs has minimal impact on the cellular metabolism of CTCs. This research provides a feasible strategy for the efficient capture and in-depth analysis of CTCs.