title: 'Stealth' nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics.
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.
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire ST5 5BG, United Kingdom. Electronic address: s.i.jenkins@keele.ac.uk.
authors.forename: Stuart I
authors.initials: SI
authors.lastname: Jenkins
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire ST5 5BG, United Kingdom. Electronic address: weinberg@hotmail.co.uk.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weinberg
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire ST5 5BG, United Kingdom. Electronic address: a.f.j.al-shakli@keele.ac.uk.
authors.forename: Arwa F
authors.initials: AF
authors.lastname: Al-Shakli
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire ST5 5BG, United Kingdom. Electronic address: a.fernandes@keele.ac.uk.
authors.forename: Alinda R
authors.initials: AR
authors.lastname: Fernandes
authors.affiliation: Chemical Engineering, School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, United Kingdom. Electronic address: H.H.Yiu@hw.ac.uk.
authors.forename: Humphrey H P
authors.initials: HHP
authors.lastname: Yiu
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire ST5 5BG, United Kingdom. Electronic address: n.d.telling@keele.ac.uk.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Telling
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire ST5 5BG, United Kingdom. Electronic address: p.roach@keele.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Roach
authors.affiliation: Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire ST5 5BG, United Kingdom. Electronic address: d.chari@keele.ac.uk.
authors.forename: Divya M
authors.initials: DM
authors.lastname: Chari
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D016503:Drug Delivery Systems; D051379:Mice; D017628:Microglia / Q000187:drug effects; D053758:Nanoparticles; D009422:Nervous System Diseases / Q000188:drug therapy*; D058953:Neural Stem Cells / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects; D011092:Polyethylene Glycols; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011092:Polyethylene Glycols
keywords: Astrocytes; Corona; Dextran (PubChem CID: 4125253); Ethylene glycol (PubChem CID: 174); Magnetite (PubChem CID: 9816051); Microglia; Neural stem cells; Oligodendrocyte precursor cells; Targeting