Functional Protein Delivery into Neurons Using Polymeric Nanoparticles

• Published in: The Journal of biological chemistry 2009-03, Vol.284 (11), p.6972-6981
• Main Authors: Hasadsri, Linda, Kreuter, Jörg, Hattori, Hiroaki, Iwasaki, Tadao, George, Julia M.
• Format: Article
• Language: English
• Subjects: Acrylic Resins - pharmacology; Animals; Cell Differentiation - drug effects; Drug Delivery Systems; Escherichia coli; Nanoparticles; Neurites - metabolism; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; PC12 Cells; Rats; Receptors, LDL - agonists; Receptors, LDL - metabolism; Recombinant Proteins - pharmacokinetics
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M805956200

An efficient route for delivering specific proteins and peptides into neurons could greatly accelerate the development of therapies for various diseases, especially those involving intracellular defects such as Parkinson disease. Here we report the novel use of polybutylcyanoacrylate nanoparticles for delivery of intact, functional proteins into neurons and neuronal cell lines. Uptake of these particles is primarily dependent on endocytosis via the low density lipoprotein receptor. The nanoparticles are rapidly turned over and display minimal toxicity to cultured neurons. Delivery of three different functional cargo proteins is demonstrated. When primary neuronal cultures are treated with recombinant Escherichia coli β-galactosidase as nanoparticle cargo, persistent enzyme activity is measured beyond the period of nanoparticle degradation. Delivery of the small GTPase rhoG induces neurite outgrowth and differentiation in PC12 cells. Finally, a monoclonal antibody directed against synuclein is capable of interacting with endogenous α-synuclein in cultured neurons following delivery via nanoparticles. Polybutylcyanoacrylate nanoparticles are thus useful for intracellular protein delivery in vitro and have potential as carriers of therapeutic proteins for treatment of neuronal disorders in vivo.