Covalent Organic Framework-Based Nanocomposite for Synergetic Photo-, Chemodynamic-, and Immunotherapies

ACS Appl Mater Interfaces. 2020 Sep 30;12(39):43456-43465. doi: 10.1021/acsami.0c12824. Epub 2020 Sep 16.

Abstract

Cancer deaths are mainly caused by tumor metastases. However, tumor ablation therapies can only target the primary tumor but not inhibit tumor metastasis. Herein, a multifunctional covalent organic framework (COF)-based nanocomposite is designed for synergetic photo-, chemodynamic- and immunotherapies. Specifically, the synthesized COF possesses the ability to produce singlet oxygen under the 650 nm laser irradiation. After being metallized with FeCl3, p-phenylenediamine is polymerized on the surface of COF with Fe3+ as the oxidant. The obtained poly(p-phenylenediamine) can be used for photothermal therapy. Meanwhile, the overexpressed H2O2 in the tumor would be further catalyzed and decomposed into hydroxyl radicals (OH) by the Fe3+/Fe2+ redox couple via Fenton reaction. Intriguingly, the increase of temperature caused by photothermal therapy can accelerate the production of OH. Moreover, the tumor-associated antigen induced a robust antitumor immune response and effectively inhibited tumor metastasis in the presence of anti-PD-L1 checkpoint blockade. Such a COF-based multifunctional nanoplatform provides an efficacious treatment strategy for both the primary tumor and tumor metastasis.

Keywords: chemodynamic therapy; covalent organic framework; immunotherapy; phototherapy; poly(p-phenylenediamine).

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / metabolism
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Ferric Compounds / chemistry
  • Ferric Compounds / pharmacology
  • Hydroxyl Radical / analysis
  • Hydroxyl Radical / metabolism
  • Immune Checkpoint Inhibitors / chemical synthesis
  • Immune Checkpoint Inhibitors / chemistry
  • Immune Checkpoint Inhibitors / pharmacology*
  • Immunotherapy
  • Metal-Organic Frameworks / chemical synthesis
  • Metal-Organic Frameworks / chemistry
  • Metal-Organic Frameworks / pharmacology*
  • Mice
  • Nanocomposites / chemistry*
  • Particle Size
  • Phenylenediamines / chemistry
  • Phenylenediamines / pharmacology
  • Photochemotherapy
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Phototherapy
  • Surface Properties

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Ferric Compounds
  • Immune Checkpoint Inhibitors
  • Metal-Organic Frameworks
  • Phenylenediamines
  • Photosensitizing Agents
  • poly(p-phenylenediamine)
  • Hydroxyl Radical