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Title: 'Stealth' nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics
Authors: Jenkins, Stuart I.
Weinberg, Daniel
Al-Shakli, Arwa F.
Fernandes, Alinda R.
Yiu, Humphrey H.
Telling, Neil D.
Roach, Paul
Chari, Divya M.
Keywords: Astrocytes
Oligodendrocyte precursor cells
Neural stem cells
Issue Date: 2016
Publisher: © Elsevier
Citation: JENKINS, S.I. ... et al, 2016. 'Stealth' nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics. Journal of Controlled Release, 224, pp. 136-145.
Abstract: Surface engineering to control cell behavior is of high interest across the chemical engineering, drug delivery and biomaterial communities. Defined chemical strategies are necessary to tailor nanoscale protein interactions/adsorption, enabling control of cell behaviors for development of novel therapeutic strategies. Nanoparticle-based therapies benefit from such strategies but particle targeting to sites of neurological injury remains challenging due to circulatory immune clearance. As a strategy to overcome this barrier, the use of stealth coatings can reduce immune clearance and prolong circulatory times, thereby enhancing therapeutic capacity. Polyethylene glycol (PEG) is the most widely-used stealth coating and facilitates particle accumulation in the brain. However, once within the brain, the mode of handling of PEGylated particles by the resident immune cells of the brain itself (the ‘microglia’) is unknown. This is a critical question as it is well established that microglia avidly sequester nanoparticles, limiting their bioavailability and posing a major translational barrier. If PEGylation can be proved to promote evasion of microglia, then this information will be of high value in developing tailored nanoparticle-based therapies for neurological applications. Here, we have conducted the first comparative study of uptake of PEGylated particles by all the major (immune and non-immune) brain cell types. We prove for the first time that PEGylated nanoparticles evade major brain cell populations — a phenomenon which will enhance extracellular bioavailability. We demonstrate changes in protein coronas around these particles within biological media, and discuss how surface chemistry presentation may affect this process and subsequent cellular interactions.
Description: This paper was accepted for publication in the journal Journal of Controlled Release and the definitive published version is available at http://dx.doi.org/10.1016/j.jconrel.2016.01.013.
Sponsor: SJ is funded by an Engineering and Physical Sciences Research Council (EPSRC; UK) Engineering Tissue Engineering and Regenerative Medicine (E-TERM) Landscape Fellowship (EP/I017801/1).
Version: Accepted for publication
DOI: 10.1016/j.jconrel.2016.01.013
URI: https://dspace.lboro.ac.uk/2134/25860
Publisher Link: http://dx.doi.org/10.1016/j.jconrel.2016.01.013
ISSN: 0168-3659
Appears in Collections:Published Articles (Chemistry)

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