4.8 Article

Polyphenol-Based Nanomedicine Evokes Immune Activation for Combination Cancer Treatment

Journal

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 4, Pages 1967-1975

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202013406

Keywords

combination cancer therapy; gossypol; metal– polyphenol coordination; nanomedicine; PD-L1 checkpoint blockade

Funding

  1. Faculty of Health Sciences, University of Macau
  2. University of Macau [SRG2018-00130-FHS]
  3. Science and Technology Development Fund, Macau SAR [0109/2018/A3, 0011/2019/AKP]

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The novel polyphenol-based nanocomplex is designed to induce highly efficacious cancer immunosurveillance, localize therapy on the primary tumor, and minimize systemic side effects. It is prepared via metal-polyphenol coordination by encapsulating natural polyphenol gossypol and a newly synthesized polyphenol derivative polyethylene glycol-Chlorin e6 (Ce6). The nanocomplex can induce chemotherapeutic/photodynamic immunogenic cancer cell death upon laser irradiation, supported by dendritic cell maturation, secretion of inflammatory cytokines, and inhibition of distant untreated tumors.
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.

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