Biologically Inspired Design of Nanoparticle Artificial Antigen-Presenting Cells for Immunomodulation

John W. Hickey, Fernando P. Vicente, Gregory P. Howard, Hai Quan Mao, Jonathan P. Schneck

Research output: Contribution to journalArticlepeer-review

Abstract

Particles engineered to engage and interact with cell surface ligands and to modulate cells can be harnessed to explore basic biological questions as well as to devise cellular therapies. Biology has inspired the design of these particles, such as artificial antigen-presenting cells (aAPCs) for use in immunotherapy. While much has been learned about mimicking antigen presenting cell biology, as we decrease the size of aAPCs to the nanometer scale, we need to extend biomimetic design to include considerations of T cell biology - including T-cell receptor (TCR) organization. Here we describe the first quantitative analysis of particle size effect on aAPCs with both Signals 1 and 2 based on T cell biology. We show that aAPCs, larger than 300 nm, activate T cells more efficiently than smaller aAPCs, 50 nm. The 50 nm aAPCs require saturating doses or require artificial magnetic clustering to activate T cells. Increasing ligand density alone on the 50 nm aAPCs did not increase their ability to stimulate CD8+ T cells, confirming the size-dependent phenomenon. These data support the need for multireceptor ligation and activation of T-cell receptor (TCR) nanoclusters of similar sizes to 300 nm aAPCs. Quantitative analysis and modeling of a nanoparticle system provides insight into engineering constraints of aAPCs for T cell immunotherapy applications and offers a case study for other cell-modulating particles.

Original languageEnglish (US)
Pages (from-to)7045-7054
Number of pages10
JournalNano Letters
Volume17
Issue number11
DOIs
StatePublished - Nov 8 2017

Keywords

  • Artificial antigen presenting cell
  • CD8+ T cell
  • immunotherapy
  • nanoparticle
  • particle size
  • receptor clustering

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

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