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Tunable Polyglycerol-Based Redox-Responsive Nanogels for Efficient Cytochrome C Delivery
Sebastian Schötz1, Felix Reisbeck1, Ann-Cathrin Schmitt1
1Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
Pharmaceutics
|August 28, 2021
Summary
Novel polyglycerol nanogels effectively deliver cytochrome C, a therapeutic protein. These redox-responsive nanocarriers protect the protein from degradation and release it in cancer cells, showing high potency and low toxicity.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery
Background:
- Therapeutic proteins are susceptible to degradation and opsonization, limiting their biomedical applications.
- Effective drug delivery systems are needed to shield proteins and enable targeted release.
- Polyglycerol-based nanogels offer a promising platform for protein encapsulation and controlled release.
Purpose of the Study:
- To synthesize novel polyglycerol-based redox-responsive nanogels.
- To evaluate their potential as nanocarriers for cytochrome C (CC) delivery.
- To assess the functionality, release kinetics, and cytotoxicity of CC-loaded nanogels.
Main Methods:
- Nanogels synthesized via inverse nanoprecipitation using inverse electron-demand Diels-Alder (iEDDA) chemistry.
- Cytochrome C (CC) encapsulated via coprecipitation, achieving high encapsulation efficiencies.
- Redox-responsive degradation triggered by l-glutathione (GSH); protein functionality and cytotoxicity assessed.
Main Results:
- High encapsulation efficiency of CC achieved within the polyglycerol nanogel network.
- Physiological reductive conditions (GSH) induced nanogel degradation, releasing 80% of CC within 48h while preserving protein functionality.
- CC-loaded nanogels demonstrated high potency against cancer cell lines (IC50 up to 30 μg·mL-1) with minimal toxicity from the free polymer.
Conclusions:
- Polyglycerol-based redox-responsive nanogels are effective carriers for therapeutic proteins like cytochrome C.
- The nanogel system protects protein cargo and enables controlled release under physiological reductive conditions.
- These nanogels show significant therapeutic potential for cancer treatment with a favorable safety profile.

