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Evaluation of Polymeric Gene Delivery Nanoparticles by Nanoparticle Tracking Analysis and High-throughput Flow Cytometry
Published on: March 1, 2013
Intercalating quaternary nicotinamide-based poly(amido amine)s for gene delivery
L J van der Aa1, P Vader2, G Storm3
1Department of Controlled Drug Delivery, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
Researchers developed novel bioreducible poly(amido amine) copolymers with intercalating quaternary nicotinamide groups for gene therapy. These polymers effectively form small, stable polyplexes with DNA, showing reduced cytotoxicity and enhanced gene expression compared to traditional cationic polymers.
Area of Science:
- Biomaterials Science
- Gene Therapy
- Polymer Chemistry
Background:
- Effective gene delivery requires polymers that form small, stable complexes with nucleic acids.
- High cationic charge density in polymers enhances complex formation but often leads to cytotoxicity.
- Alternative strategies for polymer-nucleic acid interaction are needed to improve safety and efficacy.
Purpose of the Study:
- To investigate nucleotide-specific binding via intercalation using bioreducible poly(amido amine) copolymers.
- To synthesize and characterize copolymers with varying degrees of intercalating quaternary nicotinamide (Nic) groups.
- To evaluate the impact of Nic groups on polyplex formation, stability, size, and non-viral gene delivery efficiency.
Main Methods:
- Synthesis of bioreducible poly(amido amine) copolymers with quaternary nicotinamide moieties.
- Characterization of polymer/pDNA complex formation, size, and stability.
- Assessment of polyplexes' non-hemolytic properties and in vitro gene transfection efficiency (GFP expression).
Main Results:
- Quaternary nicotinamide moieties effectively promoted self-assembled polyplex formation at low polymer/DNA ratios.
- Polyplexes formed exhibited decreased size and increased stability.
- Nicotinamide-containing polymers demonstrated non-hemolytic behavior, indicating cell membrane compatibility.
- Polymers with 25% Nic showed significantly enhanced GFP expression compared to linear PEI at lower doses.
Conclusions:
- Intercalation of quaternary nicotinamide groups provides an effective alternative to high cationic charge for polymer/pDNA complexation.
- These novel bioreducible copolymers offer improved safety profiles and enhanced gene delivery efficiency.
- N-phenylation of nicotinamide further optimizes polyplex formation and reduces required polymer dosage.
