Engineering Revolution of Cell Membrane-Biomimetic Nanoparticles: From Hybridization Strategy Innovation to Microfluidics-Enabled Precision Fabrication

• • Hybrid cell membrane-lipid nanoparticles (CM-LNPs) integrate natural membrane proteins with synthetic phospholipids, achieving synergistic retention of biological functions (e.g., immune evasion, homing) and synthetic advantages (e.g., tunable surface chemistry), as evidenced by references to RBC membrane-coated liposomes (Ferrel et al., ACS Appl Bio Mater, 2021) and tumor cell-derived vesicle-coated nanocarriers (Bose et al., ACS Nano, 2018). • • Microfluidic fabrication offers precise control over nanoparticle size and surface properties, overcoming batch-to-batch variability inherent in extrusion and ultrasonication, which is critical for scalable clinical production (reference to microfluidics-prepared ultra-small biomimetic nanovesicles for brain tumor targeting, Wang et al., 2021). • • Cell membrane biomimetic nanoparticles exhibit prolonged systemic circulation and enhanced target site accumulation via self-recognition mechanisms, with RBC membranes providing superior biocompatibility and high drug loading capacity, as demonstrated in studies on ferrimagnetic nanochain-engineered mesenchymal stem cells for post-stroke recovery (Zhang et al., Adv Funct Mater, 2019, 29:1900603). • • The homing effect of cell membranes, mediated by surface receptors responding to pathological signals, is leveraged for targeted delivery; for example, ICAM-1 functions as an efferocytosis receptor in inflammatory macrophages (Wiesolek et al., Am J Pathol, 2020, 190:874–885), and IL-1β enhances MSC adhesion via LFA-1/ICAM-1 interaction (Wu et al., Stem Cells Int, 2019), enabling inflammation-targeted delivery.