Metal-Organic Framework-Integrated Enzymes as Bioreactor for Enhanced Therapy against Solid Tumor via a Cascade

Jing Bai1, Chengjia Peng1, Liping Guo1

  • 1Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province, Key Laboratory of Polyoxometalate Science of Ministry of Education, National & Local United Engineering Laboratory for Power Batteries, Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin 130024, People's Republic of China.

Insights

This study introduces a novel bioreactor (ZIF-8@Gox/HRP) for cancer therapy. It uses enzymes to generate toxic radicals, effectively suppressing tumors and offering a new approach for safe and efficient treatments.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Natural enzyme-based cancer therapy shows promise but suffers from poor stability and delivery.
  • Limitations include low operational stability, inefficient delivery, and short enzyme lifetimes.

Purpose of the Study:

  • To develop a stable and efficient enzyme-based bioreactor for synergistic cancer therapy.
  • To overcome the limitations of natural enzymes in catalytic cancer treatment.

Main Methods:

  • Fabrication of a zeolitic imidazolate framework-8 (ZIF-8) bioreactor encapsulating glucose oxidase (Gox) and horseradish peroxidase (HRP) (ZIF-8@Gox/HRP).
  • Utilizing the bioreactor for a cascade catalytic reaction to generate reactive oxygen species for tumor treatment.

Main Results:

  • The ZIF-8@Gox/HRP bioreactor consumed endogenous glucose to produce gluconic acid and hydrogen peroxide (H2O2).
  • Encapsulated HRP decomposed H2O2 to generate highly toxic hydroxyl radicals (•OH), inducing cancer cell apoptosis.
  • In vivo studies demonstrated a significant tumor-suppression rate attributed to the cascade reaction.

Conclusions:

  • The developed ZIF-8@Gox/HRP bioreactor offers a stable and efficient platform for enzyme-based cancer therapy.
  • This approach provides a new strategy for designing smart, enzyme-based platforms for safe and effective cancer treatment.