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Updated: Jan 16, 2026
09:57
A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles
Published on: December 23, 2016
9.3K
Nitroreductase (NTR)-Triggered Degradable Polymeric Sulfur Dioxide (SO2) Prodrug.
Sagar Bag1, Desoshree Ghosh1, Arunava Seth2
1Polymer Research Centre and Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur - 741246, Nadia, West Bengal, India.
Biomacromolecules
|October 3, 2025
Summary
A novel polyurethane polyprodrug system releases sulfur dioxide (SO2) in response to nitroreductase (NTR) enzymes, offering a new approach for enzyme-responsive gas therapy in hypoxic conditions.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Nanomedicine
Background:
- Hypoxic tumor microenvironments present challenges for cancer therapy.
- Enzyme-responsive drug delivery systems offer targeted therapeutic strategies.
- Gas therapy, particularly using sulfur dioxide (SO2), is an emerging anticancer modality.
Purpose of the Study:
- To develop a nitroreductase (NTR)-responsive, sulfur dioxide (SO2)-releasing polyprodrug system.
- To investigate the self-assembly and enzyme-triggered degradation of the polyprodrug.
- To evaluate the anticancer efficacy of the developed system under hypoxic conditions.
Main Methods:
- Synthesis and characterization of amphiphilic polyurethanes.
- Investigation of self-assembly using size exclusion chromatography (SEC) and hydrodynamic diameter (Dh) measurements.
- Synthesis of NTR and SO2-responsive fluorescent probes and analysis by 1H NMR and fluorescence spectroscopy.
- Encapsulation of hypoxia-activated drug tirapazamine (TPZ) and assessment of drug release kinetics.
- Evaluation of anticancer activity using a hypoxia mimetic mediator (CoCl2).
Main Results:
- The polyprodrug system demonstrated self-assembly characteristics and enzyme-triggered degradation.
- Responsive fluorescent probes confirmed NTR and SO2 responsiveness.
- Significant release of tirapazamine (TPZ) (63%) was observed at pH 6.0 in the presence of NTR.
- The polyprodrug and TPZ-loaded nanoaggregates exhibited potent anticancer activity.
Conclusions:
- The NTR-responsive degradable polyprodrug system effectively releases SO2 and anticancer drugs under hypoxic conditions.
- This system shows promise for enzyme-responsive gas therapy and anticancer treatment.
- The study provides a new perspective on developing advanced polyprodrug systems for cancer therapy.
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