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Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
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High transfection efficiency promoted by tailor-made cationic tri-block copolymer-based nanoparticles
Rosemeyre A Cordeiro1, Daniela Santo2, Dina Farinha2
1CEMUC, Department of Chemical Engineering, University of Coimbra, 3030-790 Coimbra, Portugal.
Acta Biomaterialia
|October 17, 2016
Summary
This study introduces a novel tri-block copolymer for gene therapy, demonstrating significantly enhanced gene expression and reduced cytotoxicity compared to existing vectors. These advanced cationic polymers offer a promising, safer alternative for effective gene delivery applications.
Area of Science:
- Biomaterials Science
- Gene Therapy
- Polymer Chemistry
Background:
- Cationic polymers are promising for gene therapy but often show high cytotoxicity.
- Developing effective and safe non-viral gene delivery vectors remains a challenge.
Purpose of the Study:
- To synthesize and evaluate a novel tri-block copolymer (PDMAEMA-b-PβAE-b-PDMAEMA) as a gene carrier.
- To assess the impact of the poly(β-amino ester) segment length on vector performance.
- To compare the efficacy and safety of the developed vector against established non-viral vectors.
Main Methods:
- Synthesis and characterization of three block copolymers with varying PβAE lengths using NMR and SEC.
- Preparation and physicochemical characterization of polyplexes (DNA/polymer complexes).
- Evaluation of biological activity including cytotoxicity and transgene expression (luciferase, GFP) in HeLa and COS-7 cells.
Main Results:
- The best polyplex formulation demonstrated 40-60 fold higher transgene expression than branched PEI and TurboFect™.
- The developed nanosystems exhibited significantly lower cytotoxicity compared to PEI and TurboFect™.
- Physicochemical characterization confirmed suitable properties for gene delivery, including reduced particle size and effective DNA protection.
Conclusions:
- The tri-block copolymer PDMAEMA-b-PβAE-b-PDMAEMA shows great potential as an effective and safe non-viral gene carrier.
- Tailoring the PβAE segment length is crucial for optimizing gene delivery performance.
- This novel block copolymer represents a significant advancement over current gene delivery vectors.
Keywords:
Block copolymerClick chemistryGene deliveryPoly(beta-amino ester)Poly[2-(dimethylamino)ethyl methacrylate]
