Functional Protein Delivery into Neurons Using Polymeric Nanoparticles

Linda Hasadsri,Jörg Kreuter,Hiroaki Hattori,Tadao Iwasaki,Julia M George

doi:10.1074/jbc.m805956200

Abstract

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 beta-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 alpha-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.

Highlights

Convergent continental margins are geologically complex, with the composite units interpreted as developing either in situ from autochthonous units (e.g. South China; Zhou et al 2006) or through accretion of allochthonous terranes (e.g. New Zealand; Wandres & Bradshaw 2005)
The aim of this paper is to present these key findings and discuss the implications of the palaeomagnetic, lithological, geochemical and geophysical datasets for the terrane accretion model and discuss why an autochthonous model of margin development is preferable
(6) There is no distinction in palaeopole latitudes between the domains prior to the proposed accretion event in the current data. With these arguments for an autochthonous rather than allochthonous margin development a tectonic history is proposed by which the composite geological units of the Antarctic Peninsula can be produced in situ

Summary

Introduction

Convergent continental margins are geologically complex, with the composite units interpreted as developing either in situ from autochthonous units (e.g. South China; Zhou et al 2006) or through accretion of allochthonous terranes (e.g. New Zealand; Wandres & Bradshaw 2005). 10 km long Target Hill) in eastern Graham Land records Carboniferous metamorphism of a Devonian igneous protolith with no evidence for later metamorphism (Millar et al 2002; Riley et al 2012b), despite being

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Results

Conclusion