DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation

Nat Nanotechnol. 2021 Feb;16(2):214-223. doi: 10.1038/s41565-020-00813-z. Epub 2020 Dec 14.


Biomaterials can improve the safety and presentation of therapeutic agents for effective immunotherapy, and a high level of control over surface functionalization is essential for immune cell modulation. Here, we developed biocompatible immune cell-engaging particles (ICEp) that use synthetic short DNA as scaffolds for efficient and tunable protein loading. To improve the safety of chimeric antigen receptor (CAR) T cell therapies, micrometre-sized ICEp were injected intratumorally to present a priming signal for systemically administered AND-gate CAR-T cells. Locally retained ICEp presenting a high density of priming antigens activated CAR T cells, driving local tumour clearance while sparing uninjected tumours in immunodeficient mice. The ratiometric control of costimulatory ligands (anti-CD3 and anti-CD28 antibodies) and the surface presentation of a cytokine (IL-2) on ICEp were shown to substantially impact human primary T cell activation phenotypes. This modular and versatile biomaterial functionalization platform can provide new opportunities for immunotherapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / therapeutic use
  • Cell Line, Tumor
  • DNA / chemistry*
  • Humans
  • Immunotherapy, Adoptive
  • Lymphocyte Activation
  • Mice
  • Nanoparticles / chemistry
  • Neoplasms / therapy
  • Proteins / chemistry
  • Proteins / immunology
  • Proteins / therapeutic use
  • Receptors, Chimeric Antigen / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation


  • Biocompatible Materials
  • Proteins
  • Receptors, Chimeric Antigen
  • DNA