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Engineering Gas-Releasing Polymersome Nanoreactors for Selective Biocatalytic Activation.

Zhezhe Li1, Suzhen Wang1, Yuzhe Ma1

  • 1School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, China.

Angewandte Chemie (International Ed. in English)
|December 13, 2025
PubMed
Summary

Engineered polymersome nanoreactors release SO2 upon glutathione stimulation, enhancing membrane permeability and selectively activating glucose oxidase for cancer cell killing. This system offers controlled biocatalysis and improved therapeutic outcomes.

Keywords:
NanoreactorsPolymer self‐assemblyPolymersomesRing‐opening polymerizationStimuli‐responsive assemblies

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Chemical Biology

Background:

  • Polymersomes are promising nanoreactors but suffer from low membrane permeability, limiting substrate exchange.
  • Enzyme encapsulation within polymersomes enables biocatalysis, but controlled activation remains a challenge.

Purpose of the Study:

  • To design a glutathione (GSH)-responsive polymersome nanoreactor system for selective intracellular biocatalytic activation.
  • To enhance polymersome membrane permeability and activate glucose oxidase (GOx) biocatalysis in response to intracellular stimuli.

Main Methods:

  • Development of GSH-responsive polymersomes encapsulating glucose oxidase (GOx).
  • Stimulation with GSH to trigger SO2 release and enhance membrane permeability.
  • In vitro studies to assess cellular uptake, selective activation, and cancer cell killing efficacy.

Main Results:

  • GSH stimulation induced SO2 release, increasing polymersome membrane permeability.
  • Biocatalytic activation of GOx and glucose conversion to H2O2 occurred selectively within GSH-overexpressed cancer cells.
  • The nanoreactors demonstrated enhanced cancer cell-killing capacity by modulating intracellular reactive oxygen species (ROS) levels.

Conclusions:

  • The developed polymersome nanoreactors exhibit selective "ON/OFF" biocatalytic activation based on intracellular GSH levels.
  • This strategy provides a novel approach for targeted drug delivery and cancer therapy.
  • The system presents a promising platform for developing advanced functional polymersome-based nanoreactors.