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

Fatemeh Esmaeili, Yuhao Leo Wu, Zongjie Wang, Abdalla Abdrabou, Vuslat B. Juska, Hossein Zargartalebi, Connor D. Flynn, Teri W. Odom, Edward H. Sargent, Shana O. Kelley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 T-cells. 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.

Original languageEnglish (US)
Pages (from-to)21554-21564
Number of pages11
JournalACS nano
Volume18
Issue number32
DOIs
StatePublished - Aug 13 2024

Funding

This study was financially supported by the National Institute of Health (grant no. 2R01GM131421-05) and the National Institute of Health Heart Failure (grant no. 610-4011400-60065204). This work made use of the NUFAB facility of Northwestern University\u2019s NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-2025633), the IIN, and Northwestern\u2019s MRSEC program (NSF DMR-1720139). We also wish to acknowledge the Centre for Pharmaceutical Oncology (CPO) at the University of Toronto for assisting with a part of flow cytometry measurements.

Keywords

  • T-cell activation
  • adoptive cell transfer
  • artificial antigen-presenting cell
  • immunotherapy
  • spiky gold nanoparticles

ASJC Scopus subject areas

  • General Materials Science
  • General Engineering
  • General Physics and Astronomy

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