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Blending Carbohydrate and Quinine-Based Polymers Imparts Colloidal Stability, Improved Performance, and Cell
Nicholas W Kreofsky1, Punarbasu Roy1, Ruma Ghosh1
1Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Biomacromolecules
|August 28, 2025
Summary
Researchers developed novel sugar-based polymers for mRNA delivery, overcoming aggregation issues common with quinine-based systems. These new materials enhance cellular uptake and transfection compared to traditional PEGylated polymers.
Area of Science:
- Polymer Chemistry
- Biomaterials Science
- Nucleic Acid Delivery
Background:
- Quinine-based polymers show potential for nucleic acid delivery but suffer from aggregation due to hydrophobicity.
- Polyethylene glycol (PEG)ylation improves colloidal stability but often reduces cellular uptake of delivery vehicles.
Purpose of the Study:
- To synthesize and evaluate novel diblock quinine polymers using carbohydrates (glucose, galactose) as hydrophilic blocks for mRNA delivery.
- To compare the efficacy of sugar-based stabilizers against PEGylated analogs for mRNA delivery vehicles.
Main Methods:
- Synthesized two diblock quinine polymers with glucose or galactose as hydrophilic segments.
- Blended diblock stabilizers with hydrophobic quinine polymers in various ratios to create 73 formulations.
- Characterized formulations for particle size, mRNA binding, cellular internalization, and transfection efficiency.
Main Results:
- 47 out of 73 formulations yielded submicron particles, indicating improved colloidal stability.
- Biophysical properties, including particle size and mRNA binding, were tunable by adjusting mixture components and ratios.
- Sugar-containing stabilizers significantly outperformed PEGylated analogs in cellular internalization and transfection efficiency.
Conclusions:
- Diblock quinine polymers utilizing carbohydrate stabilizers offer a promising alternative to PEGylation for mRNA delivery.
- These novel stabilizers enhance cellular uptake and transfection, with potential for cell-specific delivery applications.
- The tunable nature of these formulations allows for optimization of mRNA delivery systems.
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