pH-Responsive Micelles Containing Quinine Functionalities Enhance Intracellular Gene Delivery and Expression
Nicholas W Kreofsky1, Punarbasu Roy1, Theresa M Reineke1
1Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States.
This study introduces quinine-functionalized polymer micelles for efficient gene delivery. Quinine enhances DNA binding and micelle disassembly, improving cellular uptake and endosomal escape for better transfection.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Gene Delivery Systems
Background:
- Quinine, a cinchona alkaloid, offers unique properties for gene delivery, including DNA binding via intercalation and electrostatic interactions.
- pH-dependent hydrophilicity/hydrophobicity of quinine influences its utility in delivery systems.
- Limited research exists on utilizing natural products like quinine in gene delivery applications.
Purpose of the Study:
- To develop and evaluate quinine-functionalized block polymer micelles for enhanced intracellular nucleic acid delivery.
- To investigate the impact of quinine incorporation into micelle core versus shell on gene delivery efficiency.
- To establish a novel platform for incorporating natural products into micellar gene delivery systems.
Main Methods:
- Synthesis of quinine-functionalized monomers (Q).
- Fabrication of self-assembled block polymer micelles with Q in core and/or shell.
- Characterization of micelle structure, DNA complexation (micelleplexes), and serum stability.
- Assessment of transfection efficiency and endosomal escape in cell lines (e.g., A549).
Main Results:
- Quinine incorporation into the micelle core facilitated acid-induced disassembly, enhancing endosomal escape and transfection efficiency, particularly in A549 cancer cells.
- Quinine in the micelle shell promoted intercalative DNA binding and formation of larger micelleplexes, increasing serum resistance and protein expression duration.
- The study demonstrates the first successful use of quinine-functionalized micelles for highly efficient gene delivery.
Conclusions:
- Quinine-functionalized block polymer micelles represent a promising strategy for efficient gene delivery.
- Strategic placement of quinine (core vs. shell) modulates micelle behavior and gene delivery outcomes.
- This work provides a versatile platform for integrating natural products into advanced micellar delivery systems.
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