T Cell-Mediated Transport of Polymer Nanoparticles across the Blood-Brain Barrier.

Ayer, Maxime; Schuster, Markus; Gruber, Isabelle; Blatti, Claudia; Kaba, Elisa; Enzmann, Gaby; Burri, Olivier; Guiet, Romain; Seitz, Arne; Engelhardt, Britta; Klok, Harm-Anton (2021). T Cell-Mediated Transport of Polymer Nanoparticles across the Blood-Brain Barrier. Advanced healthcare materials, 10(2), e2001375. Wiley 10.1002/adhm.202001375

[img]
Preview
Text
adhm.202001375.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (2MB) | Preview

Delivery of therapeutics to the central nervous system (CNS) is challenging due to the presence of the blood-brain barrier (BBB). Amongst various approaches that have been explored to facilitate drug delivery to the CNS, the use of cells that have the intrinsic ability to cross the BBB is relatively unexplored, yet very attractive. This paper presents a first proof-of-concept that demonstrates the feasibility of activated effector/memory CD4+ helper T cells (CD4+ TEM cells) as carriers for the delivery of polymer nanoparticles across the BBB. This study shows that CD4+ TEM cells can be decorated with poly(ethylene glycol)-modified polystyrene nanoparticles using thiol-maleimide coupling chemistry, resulting in the immobilization of ≈105 nanoparticles per cell as determined by confocal microscopy. The ability of these cells to serve as carriers to transport nanoparticles across the BBB is established in vitro and in vivo. Using in vitro BBB models, CD4+ TEM cells are found to be able to transport nanoparticles across the BBB both under static conditions as well as under physiological flow. Finally, upon systemic administration, nanoparticle-modified T cells are shown to enter the brain parenchyma of mice, demonstrating the brain delivery potential of this T cell subset in allogeneic hosts.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Gruber, Isabelle Manuela; Blatti, Claudia; Kaba, Elisa; Enzmann, Gaby and Engelhardt, Britta

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2192-2659

Publisher:

Wiley

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

25 Jan 2021 11:08

Last Modified:

31 Jan 2021 02:58

Publisher DOI:

10.1002/adhm.202001375

PubMed ID:

33241667

Uncontrolled Keywords:

blood-brain barriers cell-mediated deliveries cell-surface modifications nanomedicines nanoparticles

BORIS DOI:

10.48350/150897

URI:

https://boris.unibe.ch/id/eprint/150897

Actions (login required)

Edit item Edit item
Provide Feedback