Polyphenol-Based Nanomedicine Evokes Immune Activation for Combination Cancer Treatment

Angew Chem Int Ed Engl. 2021 Jan 25;60(4):1967-1975. doi: 10.1002/anie.202013406. Epub 2020 Nov 24.

Abstract

Engineering multifunctional nanoplatforms with high therapeutic benefits has become a promising strategy for intractable cancer treatment. A novel polyphenol-based nanocomplex was designed to evoke highly efficacious cancer immunosurveillance while localizing therapy on the primary tumor and to minimize systemic side effects. This nanocomplex is prepared via metal-polyphenol coordination by encapsulating a natural polyphenol, gossypol, and a newly synthesized polyphenol derivative, polyethylene glycol-Chlorin e6 (Ce6). The combination of gossypol from cotton and the photosensitizer Ce6 can induce chemotherapeutic/photodynamic immunogenic cancer cell death upon laser irradiation, which is supported by a rich maturation of dendritic cells, concentrated secretion of inflammatory cytokines, and significant inhibition of distant untreated tumors. Finally, an assistance of the programmed-cell-death ligand-1 checkpoint-blockade immunotherapy can enhance the anti-tumor immune stimulation of our nanoplatform to a higher level.

Keywords: PD-L1 checkpoint blockade; combination cancer therapy; gossypol; metal-polyphenol coordination; nanomedicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • B7-H1 Antigen / immunology
  • Cell Death / drug effects
  • Combined Modality Therapy
  • Humans
  • Immunotherapy
  • Nanomedicine*
  • Nanoparticles / therapeutic use
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Photosensitizing Agents / therapeutic use
  • Polyphenols / chemistry*

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • CD274 protein, human
  • Photosensitizing Agents
  • Polyphenols