Cell Membrane-Coated Nanoparticles as Biomimetic Drug Delivery Systems: Design, Therapeutic Applications, and Translational Challenges

Biomimetic cell membrane-coated nanoparticles (CM-NPs) have emerged as a promising class of nanocarriers that integrate the tunable physicochemical properties of engineered nanoparticles with selected biological features of naturally derived cell membranes. By retaining membrane-associated proteins, lipids, glycans, and receptors, CM-NPs have demonstrated the potential to modulate immune recognition, prolong systemic circulation, improve biocompatibility, and facilitate disease-specific targeting; however, these effects depend on the membrane source, nanoparticle composition, coating integrity, fabrication method, and biological context. This review critically examines major membrane-engineering strategies, including lipid insertion, covalent conjugation, metabolic glycoengineering, and genetic modification, together with fabrication methods such as extrusion, sonication, electroporation, in situ polymerization, and microfluidics. Particular emphasis is placed on nanoparticles coated with erythrocyte, platelet, stem cell, immune cell, bacterial, cancer cell, and hybrid membranes. Their therapeutic applications are critically evaluated, with a primary focus on cancer therapy, including photothermal and photodynamic approaches, alongside applications in cardiovascular, neurological, infectious, inflammatory, and regenerative diseases. Recent CM-NP platforms are systematically summarized according to membrane source, therapeutic cargo or nanoparticle core, disease application, and major outcomes, while recent patents are discussed to highlight emerging technological and translational developments. Despite encouraging preclinical findings, clinical translation remains constrained by challenges in membrane isolation and purification, batch reproducibility, manufacturing scalability, preservation of membrane integrity and functionality, quality control, long-term stability, biosafety, and regulatory standardization. Advances in membrane engineering, hybrid membrane systems, scalable manufacturing, standardized characterization, and rigorous safety evaluation will be important for advancing CM-NPs toward clinical translation.