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Cancer gene therapy would greatly benefit from the possibility to deliver therapeutic genes via tumor-targeted systemic intravenous delivery. The main objective of this study was to determine biophysical, transfection, and pharmacokinetic properties of DNA complexes with reducible polycations that are reversibly stabilized by surface coating with multivalent HPMA copolymers. The specific goals were to evaluate compatibility of these polyplexes with extended plasma circulation, molecular targeting, and ultrasound-enhanced transfection activity. It was demonstrated that using polyplexes based on reducible polycations allows increasing transfection activity and preserving extended plasma circulation half-life observed for control polyplexes based on non-reducible polycations. In addition, the reversibly stabilized polyplexes were compatible with both molecular targeting using protein ligands as well as physical targeting using ultrasound-directed cavitation in vitro. As such, the described gene delivery vectors have the potential to permit efficient systemic delivery of therapeutic genes targeted by a local focused ultrasound treatment.

Original publication

DOI

10.1016/j.jconrel.2005.05.002

Type

Journal article

Journal

J Control Release

Publication Date

02/09/2005

Volume

106

Pages

416 - 427

Keywords

Animals, DNA, Drug Stability, Female, Methacrylates, Mice, Mice, Inbred BALB C, Polyethyleneimine, Polylysine, Rats, Transfection, Ultrasonics