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Enhancing pDNA Delivery with Hydroquinine Polymers by Modulating Structure and Composition.
Punarbasu Roy1, Nicholas W Kreofsky1, Mary E Brown2
1Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States.
JACS Au
|July 28, 2023
Summary
Researchers developed novel quinine-based polymers for effective gene delivery. Certain polymer compositions (HQ-25 and HQ-35) showed superior transgene expression and sustained gene delivery, outperforming commercial options.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Gene Therapy
Background:
- Quinine, a natural product, shows potential for nucleic acid delivery due to its DNA-binding properties.
- Limited research exists on quinine-based polymers for gene delivery applications (transfection).
Purpose of the Study:
- To synthesize and characterize a series of hydroquinine-functionalized polymers (HQ-X) for nucleic acid delivery.
- To evaluate the efficacy of these polymers in gene delivery and understand structure-property relationships.
Main Methods:
- Synthesis of seven HQ-X polymers with varying hydroquinine (HQ) content (12-100%).
- Development of a flow cytometry assay to analyze polymer-pDNA complexes (polyplexes).
- Assessment of polyplex characteristics, including pDNA loading, protein adsorption, and cellular uptake.
- Confocal imaging to evaluate endosomal escape and pDNA-lysosome colocalization.
Main Results:
- Polymer composition significantly impacts polyplex characteristics and transfection efficiency.
- HQ-25 and HQ-35 polymers demonstrated maximum transgene expression, outperforming commercial controls and sustaining expression over 96 hours.
- Polymers with higher HQ content (HQ-44, HQ-60, HQ-100) delivered pDNA but failed to induce expression, suggesting pDNA release is a bottleneck.
- HQ-X polymers exhibited remarkable endosomal escape capabilities.
Conclusions:
- Hydroquinine-functionalized polymers (HQ-X) are promising candidates for nucleic acid delivery vehicles.
- Optimizing polymer composition and monomer structure is crucial for enhancing gene delivery efficiency.
- This study provides guiding principles for developing next-generation natural product-based gene delivery systems.
