Chiral coordination polymer nanowires boost radiation-induced in situ tumor vaccination

Nat Commun. 2024 May 9;15(1):3902. doi: 10.1038/s41467-024-48423-w.

Abstract

Radiation-induced in situ tumor vaccination alone is very weak and insufficient to elicit robust antitumor immune responses. In this work, we address this issue by developing chiral vidarabine monophosphate-gadolinium nanowires (aAGd-NWs) through coordination-driven self-assembly. We elucidate the mechanism of aAGd-NW assembly and characterize their distinct features, which include a negative surface charge, ultrafine topography, and right-handed chirality. Additionally, aAGd-NWs not only enhance X-ray deposition but also inhibit DNA repair, thereby enhancing radiation-induced in situ vaccination. Consequently, the in situ vaccination induced by aAGd-NWs sensitizes radiation enhances CD8+ T-cell-dependent antitumor immunity and synergistically potentiates the efficacy immune checkpoint blockade therapies against both primary and metastatic tumors. The well-established aAGd-NWs exhibit exceptional therapeutic capacity and biocompatibility, offering a promising avenue for the development of radioimmunotherapy approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / immunology
  • Cell Line, Tumor
  • Female
  • Gadolinium / chemistry
  • Gadolinium / pharmacology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Nanowires* / chemistry
  • Neoplasms / immunology
  • Polymers* / chemistry
  • Vaccination / methods

Substances

  • Polymers
  • Gadolinium
  • Cancer Vaccines