A Zwitterionic-Shielded Carrier with pH-Modulated Reversible Self-Assembly for Gene Transfection

Area of Science:

• Biomaterials Science
• Gene Therapy
• Polymer Chemistry

Background:

• Cationic vectors are effective for gene delivery but exhibit high cytotoxicity.
• Developing safer and more efficient gene delivery systems is crucial.

Purpose of the Study:

• To design and evaluate core-shell polyplexes with a zwitterionic shell for reduced cytotoxicity and enhanced gene delivery.
• To investigate the pH-sensitive properties and biocompatibility of these novel polyplexes.

Main Methods:

• Synthesis of poly(acrylic acid)-block-poly(sulfobetaine methacrylate) (PAA-b-PSBMA) diblock copolymers.
• Formation of core-shell polyplexes using PEI or PDMAEMA as the core and PAA-b-PSBMA as the shell.
• Gel retardation and ethidium bromide displacement assays for complexation analysis.
• In vitro assays including cytotoxicity, hemocompatibility, and transfection efficiency (β-galactosidase assay) at different pH values.

Main Results:

• The zwitterionic shell effectively reduced cytotoxicity and improved hemocompatibility (lower hemolysis, longer clotting time).
• The PAA segments provided pH sensitivity, enabling core deshielding at acidic pH (6.5).
• Transfection efficiency was significantly higher at pH 6.5 compared to pH 7.0, supported by favorable physicochemical properties.

Conclusions:

• The designed core-shell polyplexes offer a potential strategy for developing efficient and non-toxic gene carriers.
• The pH-sensitive zwitterionic shell enhances both safety and efficacy of gene delivery systems.