Engineering Revolution of Cell Membrane-Biomimetic Nanoparticles: From Hybridization Strategy Innovation to Microfluidics-Enabled Precision Fabrication
The continuous advancement of bionanomaterial technology has driven significant strategic transformations in the design and fabrication of biomimetic nanocarriers. This review systematically traces the evolution from single-cell membrane nanovesicles to hybrid cell membrane nanovesicles integrating multiple cell membranes, culminating in cell membrane hybrid lipid nanoparticles (CM-LNPs) that combine natural cell membranes or membrane proteins with engineered synthetic phospholipids. This technological progression enables the synergistic retention of multicellular biological functions while incorporating advantageous synthetic material properties, such as enhanced engineering flexibility and surface modifiability. The article critically evaluates the advantages and limitations of traditional extrusion and ultrasonication methods for preparing cell membrane nanovesicles, highlighting the benefits and development prospects of novel microfluidic techniques in CM-LNP fabrication. Furthermore, it explores future application prospects and challenges of CM-LNPs in the biomedical field, particularly in drug delivery systems and precision medicine. The review underscores the potential of CM-LNPs to overcome clinical limitations of conventional liposomes, such as poor stability, rapid drug leakage, and inadequate targeting, by leveraging the natural homing effect of cell membranes and the tunability of synthetic lipids. Emphasis is placed on the role of microfluidics in achieving precise, scalable, and reproducible fabrication, which is critical for clinical translation. The abstract synthesizes current knowledge and identifies key research gaps, offering a forward-looking perspective on the engineering of biomimetic nanoparticles for advanced therapeutic applications.