SLIDE 11
Cameron Evans Winner of 2012 GRS Prize for Research Achievement (Biological Sciences)
An ¡award ¡ceremony ¡and ¡lunch ¡will ¡ be ¡held ¡in ¡the ¡Banquet ¡Hall ¡of ¡the ¡ University ¡Club ¡on ¡the ¡2nd ¡of ¡August ¡ 2012
ACS Nano 5, 8640 (2011) (IF = 11.4)
The University of Western Australia
School of Chemistry & Biochemistry
Other School matters
SCHOOL MEETING – JULY 30 2012
Multimodal Analysis of PEI-Mediated Endocytosis of Nanoparticles in Neural Cells
Cameron W. Evans,†,‡ Melinda Fitzgerald,‡ Tristan D. Clemons,†,‡ Michael J. House,§ Benjamin S. Padman,^ Jeremy A. Shaw,^ Martin Saunders,^ Alan R. Harvey,
)
Bogdan Zdyrko,# Igor Luzinov,# Gabriel A. Silva,4,3 Sarah A. Dunlop,‡ and K. Swaminathan Iyer†,*
†School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley WA 6009, Australia, ‡Experimental
and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Australia, §School of Physics, The University of Western Australia, Australia, ^Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Australia,
)
School of Anatomy and Human Biology, The University of Western Australia, Australia, #School of Materials Science and Engineering, Clemson University, Clemson, South Carolina 29634, United States,
4Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States, and 3Department of
Ophthalmology, University of California, San Diego, Jacobs Retina Center, 9415 Campus Point Drive, La Jolla, California 92037, United States
T
he use of nanoparticles for site- specific delivery of therapeutic pay- loads is a goal that has attracted considerable attention in biomedical research.1,2 The potential ability to load a single nanoparticle preparation with a vari- ety of drugs and facilitate delivery to specific intracellular or extracellular sites would be a significant advance, because the nanoparticle delivery strategy is gener- alizable and can be used to release low molecular mass compounds, proteins, and recombinant DNAs at focal areas of disease, maximizing clinical benefits while limiting side effects.2,3 Recent reports also suggest that nanoparticles can influence cellular signaling by interacting with membrane microdomains that house different signal- ing components such as receptors, signal activators, and transducers.2,46 Because the response to this activation includes changes to cellular transport and target- ing, a precise understanding of the entire intracellular nanoparticle itinerary, beyond the point of initial entry, is important to fully realize the potential of these nano- materials as drug carriers and transfection agents.
ABSTRACT
Polymer nanoparticles are widely used as a highly generalizable tool to entrap a range of different drugs for controlled or site-specificrelease. However, despite numerous studies examining the kinetics
- f controlled release, the biological behavior of such nanoparticles remains poorly understood,
particularlywithrespecttoendocytosisandintracellulartrafficking.Wesynthesizedpolyethylenimine- decorated polymer nanospheres (ca. 100250 nm) of the type commonly used for drug release and used correlated electron microscopy, fluorescence spectroscopy and microscopy, and relaxometry to trackendocytosisinneuralcells.Thesecapabilitiesprovideinsightintohowpolyethyleniminemediates the entry of nanoparticles into neural cells and show that polymer nanosphere uptake involves three distinct steps, namely, plasma membrane attachment, fluid-phase as well as clathrin- and caveolin- independent endocytosis, and progressive accumulation in membrane-bound intracellular vesicles. These findings provide detailed insight into how the intracellular delivery of nanoparticles is mediated by polyethylenimine, which is presently the most commonly used nonviral gene transfer agent. This fundamental knowledge may also assist in the preparation of next-generation nonviral vectors.
KEYWORDS: nanosphere . endocytosis . neuron . polyethylenimine . multimodal imaging
ARTICLE
