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Redox-Responsive Polyurethane Nanonetworks with Tunable Cross-linking: A Robust Platform for Cocktail Chemotherapy
Soumya Kolay1, Madhuchhanda Das2, Sananda Dey3
1Department of Chemistry, University of Calcutta, 92 A. P. C. Road, Kolkata, West Bengal 700009, India.
Biomacromolecules
|December 19, 2025
Summary
This study presents a novel nanonetwork for targeted cancer chemotherapy. The nanonetwork selectively releases drugs within cancer cells, enhancing efficacy and reducing toxicity for improved combination therapy outcomes.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Polymer Chemistry
Background:
- Developing targeted drug delivery systems is crucial for effective cancer chemotherapy.
- Conventional chemotherapy faces challenges with off-target toxicity and limited drug release at the tumor site.
- Polymeric nanonetworks offer potential for controlled drug delivery and enhanced therapeutic efficacy.
Purpose of the Study:
- To formulate and evaluate a novel amphiphilic polyurethane nanonetwork for targeted cancer chemotherapy.
- To investigate the drug release mechanism, cellular uptake, and cytotoxicity of the nanonetwork.
- To assess the therapeutic potential of a dual-drug-loaded nanonetwork for combination therapy.
Main Methods:
- Synthesis of an amphiphilic polyurethane nanonetwork with tertiary amine and pyridyl disulfide groups.
- Investigation of reductive cleavage of disulfide linkages for sustained drug release.
- Flow cytometry analysis to assess selective cancer cell uptake based on surface charge.
- In vitro evaluation of cytotoxicity and therapeutic outcomes of single- and dual-drug-loaded nanonetworks in cancer and normal cell lines.
Main Results:
- The nanonetwork demonstrated sustained and site-specific drug release via reductive cleavage in cancer cells.
- Positive surface charge generation under acidic conditions promoted selective uptake by cancer cells (HeLa, MDA-MB-231) over normal cells.
- NN@DOX treatment showed potent cytotoxicity in cancer cells with minimal toxicity to normal cells.
- Dual-drug-loaded NN@DOX-CPT exhibited significantly enhanced therapeutic efficacy (lower IC50) compared to single-drug formulations.
Conclusions:
- The developed polymeric nanonetwork is a promising platform for targeted chemotherapy.
- The system enables site-specific drug release and selective cancer cell uptake, minimizing off-target toxicity.
- Combination drug delivery via this nanonetwork shows superior therapeutic outcomes, highlighting its potential for advanced cancer treatment.
