Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy

Nat Commun. 2016 Aug 17:7:12499. doi: 10.1038/ncomms12499.

Abstract

Advanced colorectal cancer is one of the deadliest cancers, with a 5-year survival rate of only 12% for patients with the metastatic disease. Checkpoint inhibitors, such as the antibodies inhibiting the PD-1/PD-L1 axis, are among the most promising immunotherapies for patients with advanced colon cancer, but their durable response rate remains low. We herein report the use of immunogenic nanoparticles to augment the antitumour efficacy of PD-L1 antibody-mediated cancer immunotherapy. Nanoscale coordination polymer (NCP) core-shell nanoparticles carry oxaliplatin in the core and the photosensitizer pyropheophorbide-lipid conjugate (pyrolipid) in the shell (NCP@pyrolipid) for effective chemotherapy and photodynamic therapy (PDT). Synergy between oxaliplatin and pyrolipid-induced PDT kills tumour cells and provokes an immune response, resulting in calreticulin exposure on the cell surface, antitumour vaccination and an abscopal effect. When combined with anti-PD-L1 therapy, NCP@pyrolipid mediates regression of both light-irradiated primary tumours and non-irradiated distant tumours by inducing a strong tumour-specific immune response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • B7-H1 Antigen / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Chlorophyll / analogs & derivatives
  • Coordination Complexes / chemistry*
  • Cytotoxicity, Immunologic
  • Disease Models, Animal
  • Drug Compounding
  • Immunity
  • Immunotherapy*
  • Inflammation / pathology
  • Lipids / chemistry
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Neoplasms / drug therapy*
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Organoplatinum Compounds / pharmacokinetics
  • Organoplatinum Compounds / pharmacology
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin
  • Photochemotherapy*
  • Polymers / chemistry*
  • Tissue Distribution

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Coordination Complexes
  • Lipids
  • Organoplatinum Compounds
  • Polymers
  • Oxaliplatin
  • Chlorophyll
  • pyropheophorbide a