Mammalian Cell Membrane Hybrid Polymersomes for mRNA Delivery

Cell membranes are structures essential to the cell function and adaptation. Recent studies have targeted cell membranes to identify their protective and interactive properties. Leveraging these attributes of cellular membranes and their application to vaccine delivery is gaining increasing prominence. This study aimed to fuse synthetic polymeric nanoparticles with cell membranes to develop cell membrane hybrid polymersomes (HyPSomes) for enhanced vaccine delivery. We designed a platform to hybridize cell membranes with methoxy-poly(ethylene glycol)-block-polylactic acid nanoparticles by using the properties of both components. The formed HyPSomes were optimized by using dynamic light scattering, transmission electron microscopy, and Förster resonance energy transfer, and their stability was confirmed. The synthesized HyPSomes replicated the antigenic surface of the source cells and possessed the stability and efficacy of synthetic nanoparticles. These HyPSomes demonstrated enhanced cellular uptake and translation efficiency and facilitated endosome escape. HyPSomes showed outstanding capabilities for the delivery of foreign mRNAs to antigen-presenting cells. HyPSomes may serve as vaccine delivery systems by bridging the gap between synthetic and natural systems. These systems could be used in other contexts, e.g., diagnostics and drug delivery.