Synergistic glycolysis disturbance for cancer therapy by a MOF-based nanospoiler

Xuemei Zeng1, Yihang Ruan1, Lun Wang2

  • 1Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China.

Biophysics Reports
|November 29, 2023
PubMed

Insights

Mannose and glucose oxidase (GOx) synergistically inhibit cancer cell glycolysis, inducing cell death. This combination, delivered via ZIF-8 nanoparticles, offers a promising strategy for cancer metabolism therapy.

Area of Science:

  • Biochemistry
  • Nanotechnology
  • Oncology

Background:

  • Cancer cells exhibit increased glycolysis for adenosine triphosphate (ATP) generation, a key hallmark.
  • Current strategies to inhibit glycolysis have limited therapeutic efficacy for clinical translation.

Purpose of the Study:

  • To investigate the synergistic effect of mannose and glucose oxidase (GOx) in inducing cancer cell death.
  • To develop a nanocarrier system for targeted delivery of mannose and GOx to tumor sites.

Main Methods:

  • Utilized biodegradable zeolitic imidazolate frameworks (ZIF-8) as nanocarriers for mannose and GOx (ZIF-8/M&G).
  • Investigated the mechanism of cell death induction, including ATP inhibition, autophagy activation, and apoptosis.
  • Evaluated therapeutic efficacy both in vitro and in vivo.

Main Results:

  • ZIF-8/M&G effectively accumulated at the tumor site with no obvious long-term toxicity.
  • GOx inhibited glycolysis by producing hydrogen peroxide and gluconic acid, while mannose disturbed sugar metabolism and reduced oxygen consumption.
  • The synergistic action of mannose and GOx led to significant cancer cell death and demonstrated excellent therapeutic efficacy.

Conclusions:

  • Combined mannose and GOx, delivered by ZIF-8 nanoparticles, effectively inhibit cancer cell glycolysis and induce cell death.
  • This synergistic approach offers a versatile strategy for targeting cancer metabolism.
  • The developed nanospolier shows potential for improved cancer treatment outcomes.

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