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A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles
Published on: December 23, 2016
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.
Abstract:
A nitroreductase (NTR)-responsive sulfur dioxide (SO2)-releasing polyurethane-based polyprodrug system is developed to execute enzyme-responsive gas therapy under hypoxic conditions. The self-assembled characteristics of the amphiphilic polyurethanes are thoroughly investigated, and their enzyme-triggered degradation is elucidated by size exclusion chromatography (SEC), hydrodynamic diameter (Dh) measurement, and microscopic study. Additionally, NTR and SO2-responsive small molecular and polymeric fluorescent probes are synthesized, and the respective responsiveness is studied by 1H NMR and fluorescence spectroscopy. Hypoxia-activated anticancer drug tirapazamine (TPZ) is encapsulated into the polymeric nanoaggregates, and 63% drug release is observed at pH 6.0 in the presence of NTR. Anticancer activity of the polyprodrug (SO2 as a cytotoxic agent) and TPZ-loaded polymeric nanoaggregate (SO2 and TPZ as cytotoxic agents) is demonstrated with cobalt chloride (CoCl2, hypoxia mimetic mediator). Overall, the present work reveals the impact of the NTR-responsive degradable polyprodrug as an anticancer therapeutic and gives a new perspective on enzyme-responsive gas therapy.
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