Light-Enhanced O2-Evolving Nanoparticles Boost Photodynamic Therapy To Elicit Antitumor Immunity

ACS Appl Mater Interfaces. 2019 May 8;11(18):16367-16379. doi: 10.1021/acsami.9b03541. Epub 2019 Apr 26.

Abstract

Breast cancer remains to show high mortality and poor prognosis in women despite of significant progress in recent diagnosis and treatment. Herein, we report the rational design of a highly efficient ultrasmall nanotheranostic agent with excellent photodynamic therapy (PDT) performance to against breast cancer and its metastasis by eliciting antitumor immunity. The ultrasmall nanoagent (3.1 ± 0.4 nm) was fabricated from polyethylene glycol modified Cu2- xSe nanoparticles, β-cyclodextrin, and chlorin e6 under ambient conditions. The resultant nanoplatform (CS-CD-Ce6 NPs) can be passively accumulated into the tumor to exhibit dramatic antitumor efficacy through the excellent PDT effect under near-infrared irradiation. The excellent PDT performance of this nanoplatform is owing to its role as a Fenton-like Haber-Weiss catalyst for the efficient degradation of H2O2 within the tumor to release hydroxyl radicals (·OH) and very toxic singlet oxygen (1O2) under irradiation. The generated vast amounts of reactive oxygen species not only killed primary tumor cells but also elicited immunogenic cell death (ICD) to release damage-associated molecular patterns (DAMPs) and induced proinflammatory M1-macrophages polarization. Thereby, antitumor immune responses against the metastasis of breast cancer were robustly evoked. Our work demonstrates that ultrasmall Cu2- xSe nanoparticle-based nanoplatform offers a promising way to prevent cancer metastasis via immunogenic effects through its excellent PDT performance.

Keywords: O2-evolving nanoparticles; antitumor immunity; hypoxia; immunogenic cell death; photodynamic therapy.

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Cell Hypoxia / drug effects*
  • Cell Hypoxia / immunology
  • Female
  • Humans
  • Hydrogen Peroxide / chemistry
  • Immunity / drug effects
  • Light
  • Metal Nanoparticles / administration & dosage*
  • Metal Nanoparticles / chemistry
  • Mice
  • Neoplasm Metastasis
  • Oxygen / chemistry
  • Photochemotherapy*
  • Xenograft Model Antitumor Assays

Substances

  • Hydrogen Peroxide
  • Oxygen