Shortwave-infrared-light-emitting probes for the in vivo tracking of cancer vaccines and the elicited immune responses

Nat Biomed Eng. 2024 Jun;8(6):726-739. doi: 10.1038/s41551-023-01083-5. Epub 2023 Aug 24.

Abstract

Tracking and imaging immune cells in vivo non-invasively would offer insights into the immune responses induced by vaccination. Here we report a cancer vaccine consisting of polymer-coated NaErF4/NaYF4 core-shell down-conversion nanoparticles emitting luminescence in the near-infrared spectral window IIb (1,500-1,700 nm in wavelength) and with surface-conjugated antigen (ovalbumin) and electrostatically complexed adjuvant (class-B cytosine-phosphate-guanine). Whole-body wide-field imaging of the subcutaneously injected vaccine in tumour-bearing mice revealed rapid migration of the nanoparticles to lymph nodes through lymphatic vessels, with two doses of the vaccine leading to the complete eradication of pre-existing tumours and to the prophylactic inhibition of tumour growth. The abundance of antigen-specific CD8+ T lymphocytes in the tumour microenvironment correlated with vaccine efficacy, as we show via continuous-wave imaging and lifetime imaging of two intravenously injected near-infrared-emitting probes (CD8+-T-cell-targeted NaYbF4/NaYF4 nanoparticles and H-2Kb/ovalbumin257-264 tetramer/PbS/CdS quantum dots) excited at different wavelengths, and by volumetrically visualizing the three nanoparticles via light-sheet microscopy with structured illumination. Nanoparticle-based vaccines and imaging probes emitting infrared light may facilitate the design and optimization of immunotherapies.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes* / immunology
  • Cancer Vaccines* / administration & dosage
  • Cancer Vaccines* / immunology
  • Cell Line, Tumor
  • Female
  • Infrared Rays
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry
  • Neoplasms / diagnostic imaging
  • Neoplasms / immunology
  • Quantum Dots / chemistry
  • Tumor Microenvironment

Substances

  • Cancer Vaccines