The potentiated checkpoint blockade immunotherapy by ROS-responsive nanocarrier-mediated cascade chemo-photodynamic therapy

Biomaterials. 2019 Dec:223:119469. doi: 10.1016/j.biomaterials.2019.119469. Epub 2019 Sep 5.

Abstract

Checkpoint inhibitors, such as anti-PD-1/PD-L1 antibodies, have been proven as a promising type of immunotherapy in a number of cancers, but the relatively low response rates limit their scope of clinical application. Here, we report the use of cascade chemo-photodynamic therapy (chemo-PDT) with reactive oxygen species (ROS)-sensitive lipid-polymer hybrid nanoparticles TKHNP-C/D to potentiate the antitumor efficacy of anti-PD-L1 antibody (aPD-L1). Under light irradiation, TKHNP-C/D not only induced photodynamic therapy (PDT) but also boosted intracellular DOX release via the rapid degradation of its hydrophobic core, promoting an efficient cascade of chemo-PDT to inhibit tumor growth by a single treatment. More importantly, the cascade chemo-PDT could evoke anticancer immune responses and efficiently synergize with aPD-L1 to generate an abscopal effect, which could simultaneously inhibit primary and distant tumor growth.

Keywords: Cancer immunotherapy; Cascade ICD-Inducing modalities; Cascade chemo-PDT; Checkpoint blockade immunotherapy; ROS-Sensitive hybrid nanoparticle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calreticulin / analysis
  • Cell Line, Tumor
  • Coculture Techniques
  • Colloids / chemistry
  • Drug Carriers / chemistry*
  • Immunotherapy / methods*
  • Lipids / chemistry
  • Mice
  • Nanomedicine / methods
  • Neoplasm Transplantation
  • Neoplasms / drug therapy*
  • Photochemotherapy / methods*
  • Photosensitizing Agents / pharmacology*
  • Polymers / chemistry
  • Reactive Oxygen Species / chemistry*

Substances

  • Calreticulin
  • Colloids
  • Drug Carriers
  • Lipids
  • Photosensitizing Agents
  • Polymers
  • Reactive Oxygen Species