Multimodal probing of T-cell recognition with hexapod heterostructures

Huang, Xiaodan; Meng, Lingyuan; Cao, Guoshuai; Prominski, Aleksander; Hu, Yifei; Yang, Chuanwang; Chen, Min; Shi, Jiuyun; Gallagher, Charles; Cao, Thao; Yue, Jiping; Huang, Jun; Tian, Bozhi

doi:10.1038/s41592-023-02165-7

Cited by 4 publications

(1 citation statement)

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“…The significance of the particle shape extends to aAPCs as well, where it profoundly influences T-cell activation. Anisotropic aAPCs, such as hexapod, ellipsoidal, , and tubular shaped particles with high aspect ratios, are shown to be more effective than isotropic, spherical aAPCs. This enhanced activation is attributed to the extended surface area, which increases the number of contact points between the T-cell and activating cues on the particles.…”

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confidence: 99%

Spiky Gold Nanoparticles, a Nanoscale Approach to Enhanced Ex Vivo T-Cell Activation

Esmaeili,

Wu,

Wang

et al. 2024

ACS Nano

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While existing synthetic technologies for ex vivo T-cell activation face challenges like suboptimal expansion rates and low effectiveness, artificial antigen-presenting cells (aAPCs) hold great promise for enhanced T-cell based therapies. In particular, gold nanoparticles (AuNPs), known for their biocompatibility, ease of synthesis, and versatile surface chemistry, are strong candidates for use as nanoscale aAPCs. In this study, we developed spiky AuNPs with branched geometries to present activating ligands to primary human Tcells. The special structure of spiky AuNPs enhances biomolecule loading capacity and significantly improves T-cell activation through multivalent binding of costimulatory ligands and receptors. Our spiky AuNPs outperform existing systems including Dynabeads and soluble activators by promoting greater polyclonal expansion of T-cells, boosting sustained cytokine production, and generating highly functional T-cells with reduced exhaustion. In addition, spiky AuNPs effectively activate and expand CD19 CAR-T cells while demonstrating increased in vitro cytotoxicity against target cells using fewer effector cells than Dynabeads. This study underscores the potential of spiky AuNPs as a powerful tool, bringing new opportunities to adoptive cell therapy applications.

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mentioning

confidence: 99%

Spiky Gold Nanoparticles, a Nanoscale Approach to Enhanced Ex Vivo T-Cell Activation

Esmaeili,

Wu,

Wang

et al. 2024

ACS Nano

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Engineered Nanotopographies Induce Transient Openings in the Nuclear Membrane

Sarikhani,

Patel,

et al. 2024

Adv Funct Materials

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Materials with engineered nano‐scale surface topographies, such as nanopillars, nanoneedles, and nanowires, mimic natural structures like viral spike proteins, enabling them to bypass biological barriers like the plasma membrane. These properties have led to applications in nanoelectronics for intracellular sensing and drug delivery platforms, some of which are already in clinical trials. Here, evidence is present that nanotopographic materials can induce transient openings in the nuclear membranes of various cell types without penetrating the cells, breaching the nucleo‐cytoplasmic barrier, and allowing uncontrolled molecular exchange across the nuclear membrane. These openings, induced by nanoscale curvature, are temporary and repaired through the Endosomal Sorting Complexes Required for Transport (ESCRT)‐mediated mechanisms. The findings suggest a potential for nano\topographic materials to temporarily breach the nuclear membrane with potential applications in direct nuclear sensing and delivery.

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Investigating immunity

2024

Nat Methods

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Multimodal probing of T-cell recognition with hexapod heterostructures

Cited by 4 publications

References 50 publications

Spiky Gold Nanoparticles, a Nanoscale Approach to Enhanced Ex Vivo T-Cell Activation

Spiky Gold Nanoparticles, a Nanoscale Approach to Enhanced Ex Vivo T-Cell Activation

Engineered Nanotopographies Induce Transient Openings in the Nuclear Membrane

Investigating immunity

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