Atomically dispersed bimetallic active sites as H2O2 self-supplied nanozyme for effective chemodynamic therapy, chemotherapy and starvation therapy

Biomater Adv. 2024 Sep:162:213919. doi: 10.1016/j.bioadv.2024.213919. Epub 2024 Jun 2.

Abstract

Tumor microenvironment (TME)-responsive chemodynamic therapy (CDT) is severely hindered by insufficient intracellular H2O2 level that seriously deteriorates antitumor efficacy, albeit with its extensively experimental and theoretical research. Herein, we designed atomically dispersed FeCo dual active sites anchored in porous carbon polyhedra (termed FeCo/PCP), followed by loading with glucose oxidase (GOx) and anticancer doxorubicin (DOX), named FeCo/PCP-GOx-DOX, which converted glucose into toxic hydroxyl radicals. The loaded GOx can either decompose glucose to self-supply H2O2 or provide fewer nutrients to feed the tumor cells. The as-prepared nanozyme exhibited the enhanced in vitro cytotoxicity at high glucose by contrast with those at less or even free of glucose, suggesting sufficient accumulation of H2O2 and continual transformation to OH for CDT. Besides, the FeCo/PCP-GOx-DOX can subtly integrate starvation therapy, the FeCo/PCP-initiated CDT, and DOX-inducible chemotherapy (CT), greatly enhancing the therapeutic efficacy than each monotherapy.

Keywords: Cascade catalysis; Chemodynamic therapy; Dual active sites; Nanozyme; Synergistic effect.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Catalytic Domain
  • Cell Line, Tumor
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacology
  • Doxorubicin* / therapeutic use
  • Glucose / metabolism
  • Glucose Oxidase* / chemistry
  • Glucose Oxidase* / metabolism
  • Humans
  • Hydrogen Peroxide* / chemistry
  • Hydrogen Peroxide* / metabolism
  • Mice
  • Neoplasms / drug therapy
  • Tumor Microenvironment / drug effects

Substances

  • Hydrogen Peroxide
  • Doxorubicin
  • Glucose Oxidase
  • Antineoplastic Agents
  • Glucose