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Polyhistidine-PEG:DNA nanocomposites for gene delivery
David Putnam1, Alexander N Zelikin, Vladimir A Izumrudov
1School of Chemical and Biomolecular Engineering and the Biomedical Engineering Program, Cornell University, 270 Olin Hall, Ithaca, NY 14850, USA.
Biomaterials
|August 19, 2003
Summary
New polyethylene glycol (PEG)-polyhistidine conjugates offer a promising approach for gene delivery, forming stable DNA complexes with low toxicity and effective transfection capabilities.
Area of Science:
- Biomaterials Science
- Gene Therapy
- Nanotechnology
Background:
- Polycation complexation with plasmid DNA is a common gene delivery method.
- Positive zeta potential of DNA complexes causes serum protein adsorption and complement activation.
- Polyethylene glycol (PEG) conjugation reduces protein adsorption and improves gene delivery vectors.
Purpose of the Study:
- To design and synthesize PEG-polyhistidine conjugates for gene delivery.
- To evaluate the characteristics and efficacy of these conjugates in forming DNA complexes.
Main Methods:
- Synthesis of two PEG-polyhistidine conjugate architectures: comb-shaped and linear A-B block copolymers.
- Formulation of plasmid DNA with the synthesized conjugates.
- Characterization of DNA complexation, hydrodynamic diameter, zeta potential, in vitro cytotoxicity, and transfection capacity.
Main Results:
- PEG content directly influenced the hydrodynamic diameter of DNA:conjugate complexes.
- Both architectures formed complexes with hydrodynamic diameters <150 nm.
- Complexes exhibited negative zeta potentials, enhanced DNA stability against hydrolysis, and low cytotoxicity.
- Transfection efficiency was comparable to DNA:polylysine complexes.
Conclusions:
- PEG-polyhistidine conjugates effectively condense plasmid DNA into stable nanocomposites.
- These conjugates demonstrate potential as safe and efficient gene delivery vehicles.
- The formulation characteristics suggest broad applicability in therapeutic nucleic acid delivery.