A modular encapsulation system for precision delivery of proteins, nucleic acids and therapeutics

Targeted nanoparticles have the potential to revolutionize therapeutics for medical applications. Here, we demonstrate the utility of a flexible precision nanovesicle delivery system for functional delivery of DNA, RNA, proteins and drugs into target cells. Nanovesicles generated by the membrane sculpting protein caveolin, termed caveospheres, can incorporate genetically-encoded cargo proteins without protein purification or can be loaded with RNA, DNA, proteins or drugs post-synthesis. Functionalized fluorescently-labeled caveospheres form a modular system that shows high stability in biological fluids, specific uptake by target-positive cells, and deliver proteins, drugs, DNA, and mRNA directly to the cytoplasm and nuclei of only the target cells. We demonstrate their application as a targeted transfection system for cells in culture, as a system to study endosomal escape, and critically, their efficacy in targeted delivery and tumor killing in vivo.