Self-assembling Pluronic®-modified polycations in gene delivery

The major premise of gene therapy is that the delivery of nucleic acids into human cells can cure cancer and viral infections. Synthetic vectors based on cationic polymers that bond with the nucleic acids via electrostatic interactions to form polyplexes, can enhance the transfection efficiency. However, polycation-DNA polyplexes often lack colloidal stability, especially at polymer cation/DNA phosphate charge ratios close to stoichiometric. We review a recent trend toward the utilization of polycations modified by conjugation with self-assembling block copolymers of poly(ethylene oxide) and poly(propylene oxide) (PEO-PPO-PEO, tradename Pluronic (R)) in gene delivery. It has emerged that Pluronicpolycation conjugates possess low cytotoxicity, can enhance stability of their polyplexes in water and serum, enhance the transfection efficiency both in vitro and in vivo, and provide more favorable biodistribution of the transfected DNA. All of these advantageous effects of the Pluronicpolycation conjugates stem from their self-assembling, colloidal properties such as surface activity, micellization, ability to bind biological membranes, and favorable hydrophilic-lipophilic balance. (c) 2006 Elsevier Ltd. All rights reserved.