Magnetically Actuated Hybrid Biomimetic Nanoparticles for High-Efficiency capture of Rare Circulating Tumor Cells in Whole Blood

The isolation of circulating tumor cells (CTCs) from whole blood is essential for early cancer diagnosis, metastasis prevention and therapeutic efficacy evaluation. However, this process encounters significant technical challenges, such as extreme rarity of CTCs, interference from complex components within the blood matrix, and heterogeneous expression of surface biomarkers on CTCs. In this study, to overcome these challenges, we developed a core-shell biomimetic magnetic nano-system referred to as RPCM-pMNPs. This system consists of a polyethyleneimine (PEI) modified Fe3O4 core, which exhibits high magnetic responsiveness, and a tri-component biomimetic membrane composed of red blood cell, platelet, and cancer cell membranes. The heterogeneous membrane fusion strategy synergistically integrates the long-term circulation capabilities of erythrocytes with the immune evasion properties derived from platelets, and tumor-homing specificity (EpCAM-independent binding). This approach exhibits a high selectivity in the homologous capturing efficiency of HepG2 cells, while simultaneously effectively minimizing the non-target adsorption of RAW264.7 cells in whole blood. Additionally, the capturing efficiency and selectivity of single-layer and dual-layer cell membrane coatings were systematically investigated. Comparisons among single-, dual-, and tri-component compositions provided valuable guidance for optimal membrane selection. The proposed platform exhibits significant potential in addressing the dual challenges of biofouling and immune clearance. Moreover, its biomarker-independent capture mechanism exhibits great promise for enhancing versatility, thereby facilitating broad applicability across various cancer types characterized by heterogeneous CTC phenotypes.