Jenkins, SI, Weinberg, D, Al-Shakli, A, Fernandes, A, Yiu, HHP, Telling, ND, Roach, P and Chari, DM (2016) 'Stealth' nanoparticles evade neural immune cells but also evade all major brain cell populations: Implications for PEG-based neurotherapeutics. J Control Release, 224. pp. 136-145.

[img]
Preview
Text
D Chari - Stealth nanoparticles evade neural immune cells but also evade all major brain cell populations - Implications for PEG based neurotheraputics.pdf - Accepted Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview

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.

Item Type: Article
Uncontrolled Keywords: Astrocytes, Microglia, Oligodendrocyte precursor cells, Neural stem cells, Targeting, Corona
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Symplectic
Date Deposited: 18 Jan 2016 10:45
Last Modified: 16 Apr 2019 15:10
URI: http://eprints.keele.ac.uk/id/eprint/1386

Actions (login required)

View Item View Item