Membrane Fusion Drives Facile Uptake of Cell Membrane-Coated Nanocarriers

Endocytosis has been the bane of the intracellular delivery efficiency of nanoscale systems. A class of delivery systems, viz., cell membrane-coated nanoparticles (CMNPs), show efficacious and even cell-selective uptake. We were interested in investigating the mechanism of interaction between cells and CMNPs, especially in the context of endocytic uptake and endosomal escape. We find that CMNPs are mainly taken up through a membrane-fusion-driven uptake pathway, bypassing endosomal entrapment and directly delivering therapeutic cargo to the cytoplasm. This fusion mechanism results in a significant enhancement in the intracellular delivery efficiency of both hydrophobic small molecules and nucleic acids as the cargo. The cargo-agnostic increase in delivery efficacy suggests a broad impact of this delivery system in diverse therapeutic areas.