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'Stealth' nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics

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posted on 21.07.2017 by Stuart I. Jenkins, Daniel Weinberg, Arwa F. Al-Shakli, Alinda R. Fernandes, Humphrey H. Yiu, Neil D. Telling, Paul Roach, Divya M. Chari
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.

Funding

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).

History

School

  • Science

Department

  • Chemistry

Published in

Journal of Controlled Release

Volume

224

Pages

136 - 145

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.

Publisher

© Elsevier

Version

AM (Accepted Manuscript)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Acceptance date

08/01/2016

Publication date

2016-01-11

Copyright date

2016

Notes

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.

ISSN

0168-3659

eISSN

1873-4995

Language

en

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