Engineering Cell Membrane-Coated Nanoparticles: A Route for Enhanced Therapeutic Efficacy

Cell membrane-coated nanoparticles (CMNPs) have emerged as versatile biomimetic nanoplatforms that inherit native membrane biofunctions, such as immune evasion, specific molecular recognition, and prolonged systemic circulation. Nevertheless, conventional CMNPs suffer from low surface ligand density and weak microenvironment responsiveness, leading to unsatisfactory functional homogeneity and restricted translational applicability. These limitations directly translate into key clinical challenges, including poor active targeting capability, rapid in vivo clearance, and insufficient tumor penetration. To tackle these material engineering limitations, engineered (ECMNPs) have been developed through modular membrane engineering to enable precise and programmable surface functionalization. This review systematically summarizes five mainstream membrane modification strategies for ECMNP construction, including stimuli-responsive functionalization, genetic engineering, covalent conjugation, noncovalent assembly, and membrane fusion. By integrating endogenous membrane bioactivity with artificially optimized nanostructures, ECMNPs exhibit tunable targeting capability, stimuli-triggered drug release, immunomodulatory effects, and enhanced transbarrier delivery for treating intractable diseases. We further discuss key translational bottlenecks regarding membrane sourcing, extraction procedures, structural stability, and biological safety. This work highlights membrane engineering-enabled biological regulation of nanomaterials, offering rational guidelines for the design and scalable fabrication of next-generation biomimetic nanotherapeutics.