The Effect of the Nanoparticle Shape on T Cell Activation

© 2022 Wiley-VCH GmbH..

The mechanism of extracellular ligand nano-geometry in ex vivo T cell activation for immunotherapy remains elusive. Herein, the authors demonstrate large aspect ratio (AR) of gold nanorods (AuNRs) conjugated on cell culture substrate enhancing both murine and human T cell activation through the nanoscale anisotropic presentation of stimulatory ligands (anti-CD3(αCD3) and anti-CD28(αCD28) antibodies). AuNRs with large AR bearing αCD3 and αCD28 antibodies significantly promote T cell expansion and key cytokine secretion including interleukin-2 (IL-2), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α). High membrane tension observed in large AR AuNRs regulates actin filament and focal adhesion assembly and develops maturation-related morphological features in T cells such as membrane ruffle formation, cell spreading, and large T cell receptor (TCR) cluster formation. Anisotropic stimulatory ligand presentation promotes differentiation of naïve CD8+ T cells toward the effector phenotype inducing CD137 expression upon co-culture with human cervical carcinoma. The findings suggest the importance of manipulating extracellular ligand nano-geometry in optimizing T cell behaviors to enhance therapeutic outcomes.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:18

Enthalten in:

Small (Weinheim an der Bergstrasse, Germany) - 18(2022), 36 vom: 27. Sept., Seite e2107373

Sprache:

Englisch

Beteiligte Personen:

Oh, Jiwon [VerfasserIn]
Xia, Xingyu [VerfasserIn]
Wong, Wai Ki Ricky [VerfasserIn]
Wong, Siu Hong Dexter [VerfasserIn]
Yuan, Weihao [VerfasserIn]
Wang, Haixing [VerfasserIn]
Lai, Chun Him Nathanael [VerfasserIn]
Tian, Ye [VerfasserIn]
Ho, Yi-Ping [VerfasserIn]
Zhang, Honglu [VerfasserIn]
Zhang, Yuan [VerfasserIn]
Li, Gang [VerfasserIn]
Lin, Yuan [VerfasserIn]
Bian, Liming [VerfasserIn]

Links:

Volltext

Themen:

Anisotropic nanomaterials
CD3 Complex
Cell membrane tension
Interleukin-2
Journal Article
Ligands
Nanoscale ligand presentation
Research Support, Non-U.S. Gov't
T cell activation

Anmerkungen:

Date Completed 09.09.2022

Date Revised 19.10.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1002/smll.202107373

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM338278303