Platelet–Leukocyte Hybrid Membrane‐Coated Immunomagnetic Beads for Highly Efficient and Highly Specific Isolation of Circulating Tumor Cells

Abstract

Biomimetic cell-membrane-camouflaged nanoparticles with desirable features have been widely used for various biomedical applications. However, the current research focuses on single cell membrane coating and using multiple cell membranes for nanoparticle functionalization is still challenging. In this work, platelet (PLT) and leukocyte (WBC) membranes are fused, PLT-WBC hybrid membranes are coated onto magnetic beads, and then their surface is modified with specific antibodies. The resulting PLT-WBC hybrid membrane-coated immunomagnetic beads (HM-IMBs) inherit enhanced cancer cell binding ability from PLTs and reduce homologous WBC interaction from WBCs, and are further used for highly efficient and highly specific isolation of circulating tumor cells (CTCs). By using spiked blood samples, it is found that, compared with commercial IMBs, the cell separation efficiency of HM-IMBs is improved to 91.77% from 66.68% and the cell purity is improved to 96.98% from 66.53%. Furthermore, by using the HM-IMBs, highly pure CTCs are successfully identified in 19 out of 20 clinical blood samples collected from breast cancer patients. Finally, the robustness of HM-IMBs is verified in downstream CTC analysis such as the detection of PIK3CA gene mutations. It is anticipated that this novel hybrid membrane coating strategy will open new possibilities for overcoming the limitations of current theranostic platforms.

Human Platelet Membrane Functionalized Microchips with Plasmonic Codes for Cancer Detection

“…The aggregation of platelets around circulating tumor cells, which facilitates the survival of these cells in the bloodstream and their spread to new tissues, is mainly caused by the binding of platelet integrin α IIb β 3 to tumor cell integrin α v β 3 via RGD motif‐containing proteins such as fibrinogen, von Willebrand factor, and fibronectin . Consequently, the presence of a unique surface protein set on platelets results in excellent multifaceted binding affinity and specificity, making them appealing alternatives to antibodies for tumor recognition . The direct interaction of platelets with cancer cell‐derived EVs is known to induce plasma clotting and platelet aggregation; however, the mechanism of this interaction and that of possible functional alterations in platelets remain unclear …”

Cell Membrane-Camouflaged Nanocarriers for Cancer Diagnostic and Therapeutic

“…The cell purity of the HM-IMBs was 96.98%, which is much higher than that of the IMBs (66.53%). HM-IMBs also proved effective in detection of PIK3CA gene mutations (Rao et al, 2018). Similarly, neutrophilmembrane-coated PLGA NPs (NM-NPs) were also developed.…”

Cancer Stem Cell‐Platelet Hybrid Membrane‐Coated Magnetic Nanoparticles for Enhanced Photothermal Therapy of Head and Neck Squamous Cell Carcinoma

“…Hence, carrying both cancer cell marker and CSC marker, CSC membrane‐coated nanoparticles could offer enhanced CSC targeting ability. However, current studies focus on independent cell membrane–coated NPs, and multifunctional hybrid membrane materials from different membrane types are still rare …”