Near-Infrared-Light Remote-Controlled Activation of Cancer Immunotherapy Using Photothermal Conjugated Polymer Nanoparticles

Adv Mater. 2021 Aug;33(34):e2102570. doi: 10.1002/adma.202102570. Epub 2021 Jul 18.

Abstract

Remote control of the therapeutic process is an ideal strategy for maximizing efficacy and avoiding side effects, especially for cancer immunotherapy. Herein, a conjugated polymer nanoparticles (CPNs)-mediated optogenetic system for in situ activation of immunotherapy under near-infrared laser irradiation is reported. This system is composed of photothermal CPNs and interferon-gamma (IFN-γ) plasmid driven by heat shock promoter HSP70. The photothermally responsive CPNs serve as a photo-heat nanotransducer to trigger the gene transcription of IFN-γ cytokine. The secreted IFN-γ from cancer cells can sufficiently elicit surrounding tumor-associated macrophages activation through IFN-γ-JAK-STAT1 transcription-factor signaling pathway and finally induce cancer cell killing by immunotherapy. Therefore, this synergetic optogenetic system provides a promising approach to remotely control the process of cancer immunotherapy.

Keywords: cancer immunotherapy; conjugated polymers nanoparticles; optogenetics; remote-controlled activation.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cytokines / metabolism
  • HSP70 Heat-Shock Proteins / chemistry
  • Hot Temperature
  • Humans
  • Immunosuppressive Agents / chemistry
  • Immunotherapy / methods*
  • Interferon-gamma / chemistry
  • Interferon-gamma / metabolism
  • Lipids / chemistry
  • Macrophage Activation
  • Macrophages / metabolism
  • Mice
  • Microscopy, Electron, Transmission
  • Nanomedicine / instrumentation
  • Nanoparticles / chemistry*
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Photochemistry
  • Polymers / chemistry*
  • Signal Transduction
  • Spectroscopy, Near-Infrared / methods*
  • Temperature
  • Tumor-Associated Macrophages / metabolism

Substances

  • Cytokines
  • HSP70 Heat-Shock Proteins
  • Immunosuppressive Agents
  • Lipids
  • Polymers
  • Interferon-gamma