Precisely Engineering Biomimetic Nanoparticles via Controlled Cell Membrane Coating

Cell membrane-coated nanoparticles (CMNPs) represent an advanced class of biomimetic nanomaterials that integrate the functional complexity of natural cell membranes with the tunable properties of synthetic nanoparticle cores. By inheriting native membrane proteins, lipids, and glycans, CMNPs exhibit attractive properties such as enhanced immune evasion, prolonged circulation, and cell-specific interactions, thereby supporting a wide range of therapeutic, diagnostic, and biomedical applications. However, precise control over CMNPs fabrication remains challenging, particularly with respect to particle size, membrane coating integrity, and membrane leaflet orientation, all of which critically influence biological performance. This review focuses on recent progress in engineering CMNPs with precise control over size, coating integrity, and membrane leaflet orientation. It first analyzes how synthetic parameters influence the particle size and size distribution of CMNPs, then outlines strategies to improve membrane coating integrity together with the corresponding evaluation methods and discusses approaches to regulate membrane leaflet orientation and the analytical techniques used for its assessment. Finally, this review highlights remaining challenges and future directions for the rational design of CMNPs, supporting their continued development toward translational nanomedicine applications.