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Methionine Functionalized Biocompatible Block Copolymers for Targeted Plasmid DNA Delivery
Published on: August 6, 2019
Plasmid DNA complexation with phosphorylcholine diblock copolymers and its effect on cell transfection
Xiubo Zhao1, ZhuoQi Zhang, Fang Pan
1Biological Physics Group, School of Physics and Astronomy, The University of Manchester, Schuster Building, Manchester M13 9PL, United Kingdom.
Langmuir : the ACS Journal of Surfaces and Colloids
|May 27, 2008
Summary
Novel cationic copolymers show that their structure and charge, influenced by pH, significantly impact gene delivery efficiency. Unimer/DNA complexes are more effective for transfecting HEK293 cells than micellar ones.
Area of Science:
- Biomaterials Science
- Gene Delivery Systems
- Polymer Chemistry
Background:
- Cationic polymers are explored as non-viral vectors for gene delivery.
- Understanding polyplex formation and its impact on transfection efficiency is crucial.
- 2-methacryloyloxyethyl phosphorylcholine (MPC)-based copolymers offer tunable properties for gene delivery.
Purpose of the Study:
- To investigate the effect of charge ratio and pH on cationic MPC-based copolymer/DNA polyplex formation.
- To correlate polyplex structure and charge distribution with gene transfection efficiency.
- To elucidate the role of copolymer hydrophobicity and pH-dependent behavior in gene delivery.
Main Methods:
- Electrophoresis, dynamic light scattering, and small-angle neutron scattering were used to characterize polyplexes.
- Luciferase plasmid DNA was complexed with various cationic MPC-based copolymers.
- HEK293 cells were used to assess gene transfection efficiency.
Main Results:
- Polymer hydrophobicity influenced pKa values and aggregation; electrostatic interactions drove nanopolyplex formation.
- pH significantly affected polyplex structure: unimers below pKa, micelles above pKa.
- Unimer/DNA polyplexes demonstrated superior transfection efficiency in HEK293 cells compared to micellar polyplexes.
Conclusions:
- Cationic MPC-based copolymer structure and charge characteristics, modulated by pH and hydrophobicity, are critical for gene delivery.
- Polyplex nanostructure (unimer vs. micelle) dictates transfection efficacy.
- This study provides insights into polyplex formation mechanisms and their link to gene delivery performance.
