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Related Experiment Video

Updated: Jun 7, 2025

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A Multi-Functional Cascade Nanoreactor for Remodeling Tumor Microenvironment to Realize Mitochondria Dysfunction via

Longhai Jin1, Shijie Zhou2,3, Tianqi Zhang1

  • 1Department of Radiology, The Second Hospital of Jilin University, Changchun, 130041, China.

Small (Weinheim an Der Bergstrasse, Germany)
|November 14, 2024
PubMed
Summary

This study introduces a novel nanoreactor that enhances cancer treatment by remodeling the tumor microenvironment (TME). The nanoreactor boosts reactive oxygen species (ROS) generation and induces mitochondrial dysfunction for improved therapeutic outcomes.

Keywords:
H2O2chemodynamic therapyphotodynamic therapyself‐supplytumor microenvironment

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Chemo/photodynamic therapy (CDT/PDT) shows promise for cancer treatment by generating reactive oxygen species (ROS) and causing mitochondrial dysfunction.
  • Tumor microenvironment (TME) factors like low H2O2, hypoxia, and high reduced glutathione (GSH) limit the efficacy of dynamic therapies.
  • Developing strategies to overcome TME limitations is crucial for enhancing anticancer treatment efficiency.

Purpose of the Study:

  • To design a multi-functional cascade nanoreactor for remodeling the TME to enhance dynamic therapy.
  • To investigate the nanoreactor's ability to induce ROS storm and Zn2+ ion overload for mitochondria dysfunction.
  • To improve the efficiency of anticancer treatment through TME modulation and enhanced ROS generation.

Main Methods:

  • A bovine serum albumin modified ZnO2@CeO2-ICG nanoreactor was synthesized.
  • The nanoreactor's decomposition of H2O2 and catalytic activity by CeO2 were analyzed.
  • Indocyanine green (ICG) was utilized for photodynamic therapy (PDT) under 808 nm light irradiation.
  • The role of GSH consumption in regenerating Ce(III) ions and enhancing CDT efficiency was studied.
  • Mitochondrial dysfunction induction via ROS and Zn2+ overload was assessed.

Main Results:

  • The nanoreactor successfully decomposed into H2O2 and Zn2+ ions within the TME.
  • CeO2 catalyzed H2O2 into ·OH and O2, while ICG generated singlet oxygen (1O2) under light, boosting PDT.
  • GSH consumption by Ce(IV) ions regenerated Ce(III) ions, enhancing CDT and alleviating ROS scavenging.
  • The combined effect of TME remodeling, elevated ROS, and Zn2+ overload led to significant mitochondria dysfunction.
  • The nanoreactor demonstrated enhanced antitumor treatment efficiency.

Conclusions:

  • The developed ZnO2@CeO2-ICG nanoreactor effectively remodels the TME to overcome therapeutic limitations.
  • This nanoreactor strategy significantly enhances dynamic therapy by creating a ROS storm and inducing mitochondria dysfunction.
  • Functional nanoreactors offer a promising approach to improve the efficacy of anticancer therapies.