PH-sensitive self-assembled carboxymethyl chitosan-modified DNA/polyethylenimine complexes for efficient gene...

Area of Science:

• Biomaterials Science
• Gene Therapy Delivery Systems
• Nanotechnology for Medicine

Background:

• Gene delivery systems require stability, low toxicity, and efficient targeting.
• Polyethylenimine (PEI) is a common gene carrier but exhibits toxicity.
• Carboxymethyl chitosan (CMCS) offers biocompatibility and pH-sensitivity.

Purpose of the Study:

• To develop novel pH-sensitive DNA/polyethylenimine/carboxymethyl chitosan ternary complexes (DPCs) for gene delivery.
• To evaluate the stability, toxicity, and transfection efficiency of DPCs.
• To investigate the pH-responsive behavior of DPCs in acidic tumor microenvironments.

Main Methods:

• Layer-by-layer self-assembly technique for DPC fabrication.
• DNA condensation, DNase I protection, and plasma stability assays.
• In vitro cytotoxicity, acute toxicity, and transfection efficiency studies under varying pH conditions.

Main Results:

• DPCs exhibited a layered structure and effective DNA condensation.
• CMCS modification improved plasma stability and reduced cytotoxicity and acute toxicity compared to binary complexes.
• DPCs demonstrated pH-sensitive layer detachment in acidic environments (pH 6.5), facilitating gene delivery in simulated tumor conditions.

Conclusions:

• CMCS modification enhances the safety and stability of DNA/polyethylenimine complexes for gene delivery.
• DPCs show promising pH-responsive behavior for targeted gene delivery in acidic tumor tissues.
• The developed DPCs offer a safe, stable, and efficient gene delivery platform with potential for clinical applications.