A Hybrid Supramolecular Polymeric Nanomedicine for Cascade-Amplified Synergetic Cancer Therapy

Angew Chem Int Ed Engl. 2022 Jul 4;61(27):e202203786. doi: 10.1002/anie.202203786. Epub 2022 May 5.

Abstract

Supramolecular nanomedicines have shown great merits in cancer therapy, but their clinical translation is hampered by monotonous therapeutic modality and unsatisfactory antitumor performance. Herein, a hybrid supramolecular polymeric nanomedicine (SNPs) is developed based on β-cyclodextrin/camptothecin (CPT) host-guest molecular recognition and iron-carboxylate coordination. Iron ions stabilizing SNPs catalyze the conversion of intracellular hydrogen peroxide into highly toxic hydroxyl radical through a Fenton reaction, which further cleaves the thioketal linker of the supramolecular monomer to release potent CPT, thus amplifying the therapeutic efficacy by combining chemodynamic therapy and chemotherapy. The combination therapy stimulates antitumor immunity and promotes intratumoral infiltration of cytotoxic T lymphocytes by triggering immunogenic cell death. In synergy with PD-L1 checkpoint blockade, SNPs enables enhanced immune therapy and a long-term tumor remission.

Keywords: Cancer Theranostics; Chemodynamic Therapy; Host-Guest Systems; Immunotherapy; Supramolecular Chemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Camptothecin / pharmacology
  • Camptothecin / therapeutic use
  • Cell Line, Tumor
  • Humans
  • Iron / therapeutic use
  • Nanomedicine
  • Nanoparticles* / therapeutic use
  • Neoplasms* / drug therapy
  • Polymers / therapeutic use
  • beta-Cyclodextrins / pharmacology
  • beta-Cyclodextrins / therapeutic use

Substances

  • Polymers
  • beta-Cyclodextrins
  • Iron
  • betadex
  • Camptothecin