Lipid‐Centric Design of Plasma Membrane‐Mimicking Nanocarriers for Targeted Chemotherapeutic Delivery

Abstract The plasma membranes (PM) of mammalian cells contain diverse lipids, proteins, and carbohydrates that are important for systemic recognition and communication in health and disease. Cell membrane coating technology that imparts unique properties of natural plasma membranes to the surface of encapsulated nanoparticles is thus becoming a powerful platform for drug delivery, immunomodulation, and vaccination. However, current coating methods fail to take full advantage of the natural systems because they disrupt the complex and functionally essential features of PMs, most notably the chemical diversity and compositional differences of lipids in two leaflets of the PM. Herein, a new lipid coating approach is reported in which the lipid composition is optimized through a combination of biomimetic and systematic variation approaches for the custom design of nanocarrier systems for precision drug delivery. Nanocarriers coated with the optimized lipids offer unique advantages in terms of bioavailability and efficiency in tumor targeting, tumor penetration, cellular uptake, and drug release. This pilot study provides new insight into the rational design and optimization of nanocarriers for cancer chemotherapeutic drugs and lays the foundation for further customization of cell membrane‐mimicking nanocarriers through systematic incorporation of other components.