Genetically Engineered Cell Membrane‐Coated Magnetic Nanoparticles for High‐Performance Isolation of Circulating Tumor Cells

Abstract

Circulating tumor cells (CTCs) are a crucial biomarker for early cancer diagnosis and progress of cancer metastasis. However, the extremely rare CTCs with large amounts of background leukocytes seriously restricte the purity of enriched CTCs. Herein, genetically engineered cell membrane‐coated magnetic nanoparticles with following properties are constructed: I) The leukocyte membrane camouflaged nanoparticles, which could significantly reduce nonspecific binding of homologous leukocytes and achieve high‐purity isolation of CTCs, are prepared by simple one‐step extrusion and II) the cellular membrane stably expressing single‐chain variable fragment (scFv) of anti‐epidermal growth factor receptor (EGFR) antibody could ensure the recognition of EGFR‐positive CTCs. The binding affinity of the resulting nanoparticles toward extracellular EGFR protein improved more than 100‐fold compared with natural cell membrane‐coated nanoparticles. Furthermore, compared with commercial immunomagnetic nanoparticles, the functional nanoparticles achieved a greater capture efficiency in artificial blood samples and the cell purity increased from 64.8% to 93.5%. Consequently, the authors successfully isolate high pure CTCs from 6 out of 6 cancer patients using engineered cell membrane‐coated nanoparticles. This platform exhibits a promising potential for CTC detection in clinical samples, offering an innovative method for cancer diagnosis and prognosis evaluation.

Cell Membrane-Coated Nanoparticles for Precision Medicine: A Comprehensive Review of Coating Techniques for Tissue-Specific Therapeutics

“…M any different cell types have been used for nanoparticle membrane coating (Table 1). Notably, a range of cancer lines has been used, including cervical and ovarian cancers [21][22][23][24], multiple myeloma [25], melanoma [12,[26][27][28][29][30][31][32], leukemia [23,[33][34][35][36][37][38][39][40][41][42][43][44], breast cancer [6,37,40,[45][46][47][48][49][50][51][52][53][54][55][56], neuroblastoma [79], colon carcinoma [23,57], head and neck squamous cell carcinoma [58][59][60][61], lung cancer…”

Engineered Cell Membrane-Camouflaged Nanomaterials for Biomedical Applications

“…This highlights that novel biomimetic magnetosomes have great potential for highly effective CTC enrichment. Chemical modification can impair the biological activity of antibodies; thus, Jiang et al used genetic engineering to construct a chimeric antibody membrane on a single-chain variable fragment (ScFv) that overexpressed epidermal growth factor receptor (EGFR) antibodies on the human leukemia T lymphocyte ( Figure 7 A) [ 121 ]. The membrane was then applied to magnetic nanoparticles (JE-CM-MNs) to enrich CTCs.…”

“…(ScFv: single-chain variable fragment; JE-CM: chimeric antibody membrane). Reprinted from [ 121 ] with permission from Wiley, copyright 2023. ( B ) The method of preparing HDFGFR4/CMMNPs.…”

Magnetic Nanoagent Coated with an Activated Macrophage Membrane for Colorimetric Detection of Bacteria

“…Cell membranes are a fluid biointerface that play crucial roles in cellular recognition and biological modulation. To fully engage the functionality of cell membranes, natural cell membrane-based architectures are manufactured by wrapping cell membranes derived from diverse cells such as cancer cells, immune cells, red blood cells (RBCs), bacteria, and others onto synthetic materials via a top-down approach. − These products inherit the desirable biofunctions of the source cells, not only providing exemplar models for investigating the complex interplay of biological systems but also facilitating their applications in viral inhibition, drug delivery, vaccine design, immunotherapy, and biosensing. − In the biosensing field, membrane proteins are often leveraged for target recognition through ligand–receptor interaction. For example, a macrophage membrane-coated electrode transducer has been constructed for TNF-α detection, where natural TNF-α receptors on the membrane are used as recognition elements .…”