The Effect of the Nanoparticle Shape on T Cell Activation
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AbstractThe 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.
Acceptance Date16/03/2022
All Author(s) ListJiwon Oh, Xingyu Xia, Wai Ki Ricky Wong, Siu Hong Dexter Wong, Weihao Yuan, Haixing Wang, Chun Him Nathanael Lai, Ye Tian, Yi-Ping Ho, Honglu Zhang, Yuan Zhang, Gang Li, Yuan Lin, Liming Bian
Journal nameSmall
Year2022
Month9
Day8
Volume Number18
Issue Number36
PublisherWiley
Article number2107373
ISSN1613-6810
LanguagesEnglish-United States
