The Effect of the Nanoparticle Shape on T Cell Activation

Abstract 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.