Genetically Engineered Membrane-Coated Nanoparticles as Versatile Platforms with Reduced Protein Corona for Targeted siRNA Delivery

Low uptake efficiency in vivo as well as systemic toxicities of nucleic-acid nanovehicles substantially retard the clinical translation of gene therapy. Targeted gene delivery to specific cell populations with antibody display techniques and membrane-coated nanoparticle (NP) approaches may solve these problems. Here, a new class of targeted membrane-camouflaged nanosystem is successfully constructed, which is made of polydopamine (PDA) nanoparticles coated with biosynthetic antibody-displaying membranes from stem cells. In murine models of rheumatoid arthritis and colitis, the membrane-camouflaged nanocarriers displayed anti-CD64 antibodies in a ligand-oriented way via the biosynthetic method and has reduced protein corona due to the coating of the negatively charged cell membrane, thereby achieving remarkable therapeutic efficacy through silencing the TNF expression selectively in CD64-positive immune cell subsets. By expressing a wide variety of functional protein ligands on the cellular membranes that are further coated onto PDA nanoparticles, the membrane-camouflaged nanosystems can also serve as a versatile theranostic platform that enables antibody-targeted gene/siRNA delivery to the cells of interest in vivo, especially immune cells. Bioengineered-membrane-cloaked polydopamine (PDA) nanoparticles (NPs) could express various protein ligands on their surface, thereby serving as an in vivo targeted gene delivery platform and achieving satisfactory gene silencing efficacy in rheumatoid arthritis and colitis models.image