Charge-Shifting Polycations Based on N,N-(dimethylamino)ethyl Acrylate for Improving Cytocompatibility During DNA...

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Gene Delivery

Background:

• Synthetic polycations are cost-effective, stable alternatives to viral vectors for DNA delivery.
• Developing non-viral vectors with improved safety and efficacy is crucial for gene therapy.

Purpose of the Study:

• To synthesize and evaluate charge-shifting polycations (PAD copolymers) for in vitro DNA delivery.
• To assess the cytotoxicity and cell uptake efficiency of PAD copolymers compared to existing non-viral vectors.

Main Methods:

• RAFT polymerization was used to synthesize PAD copolymers with controlled molecular weights.
• Hydrolysis studies determined the charge-shifting rates of the polycations.
• In vitro studies evaluated cell viability and DNA polyplex uptake in HeLa cells.

Main Results:

• PAD copolymers exhibited tunable charge-shifting hydrolysis, forming polyampholytes.
• PAD copolymers showed comparable or higher cell viability than non-charge-shifting polycations and PEI.
• Cell uptake efficiency of PAD/DNA polyplexes exceeded that of PEI polyplexes.

Conclusions:

• PAD copolymers, particularly PAD80, demonstrate suitable charge-shifting hydrolysis for DNA delivery.
• Reduced cytotoxicity and high uptake efficiency make PAD copolymers a promising non-viral gene delivery system.
• The resulting polyampholytes may enhance long-term cytocompatibility.