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.

The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity

“…Similarly, an in situ injectable hydrogel has been constructed via single-step equal volume mixing of a PBS solution of oxidized HA and hydrazide grafted gelatin, and its immunomodulatory function by the release of sEVs overexpressing PD-L1 in bone regeneration has been verified [ 143 ]. Additionally, with the rapid development of bio-nanotechnology, various nano-structured materials in soft materials, such as anisotropic nanoscale ligands [ 248 ] and composite nanoparticles [ 249 ], have also been applied to regulate cell behaviors and promote bone regeneration. For example, Wong et al [ 250 ] have conjugated RGD-bearing magnetic nanoparticles (Fe 3 O 4 coated with silica) to increase RGD tether mobility, which can be decreased through the application of an external magnetic field, thus increasing MSC adhesion, spreading, and osteogenic differentiation.…”

Nanomanipulation of Ligand Nanogeometry Modulates Integrin/Clathrin-Mediated Adhesion and Endocytosis of Stem Cells

“…Before nanosubstrate fabrication, we replaced the CTAB surfactant of AR4 with citrate by ligand exchange (Figure S1). 39,40 This successful modification was confirmed by ultraviolet−visible absorption spectroscopy, which showed similar SPR peaks (Figure S1B) and consecutive changes of zeta potentials throughout the exchange (Figure S1C). Next, we engineered the nanosubstrate by employing mercaptopropylsilatrane (MPS) for thiolation, followed by immobilizing AR1 or AR4 onto the thiolated substrate via Authiol linkages, forming AR1-S or AR4-S, respectively (Figure 1A).…”

Particle-Based Artificial Antigen-Presenting Cell Systems for T Cell Activation in Adoptive T Cell Therapy

“…The primary goal of altering the particle morphology is to augment the contact area between T cells and aAPCs, thereby enhancing the TCR signaling. 31,71,139 In general, at similar particle size, nonspherical nanoscale aAPCs with higher aspect ratios and larger radii of curvature exhibit a larger contact area with T cells compared to their spherical counterparts, therefore promoting the formation of larger immune synapses. 99,140 They also exhibit enhanced in vivo drainage properties, allowing them to easily enter lymph nodes through lymphatic drainage.…”