Accelerated gene transfer through a polysorbitol-based transporter mechanism

Abstract

Here we report an accelerated gene transfer through a polysorbitol-based osmotically active transporter (PSOAT) that shows several surprising results through interesting mechanisms. The nano-sized and well-complexed PSOAT/DNA particles are less toxic, stable at serum and show no aggregation after lyophilization due to their polysorbitol backbone. The transfection is remarkably accelerated both in vitro and in vivo, presumably due to a transporter mechanism of PSOAT in spite of possibility of reduction of transfection by many hydroxyl groups in the transporter. PSOAT possesses a transporter mechanism owing to its polysorbitol backbone, which enhances cellular uptake by exerting polysorbitol transporter activity, thus accelerates gene transfer to cells because transfection ability of PSOAT is drastically reduced in the presence of a cyclooxygenase (COX)-2-specific inhibitor, which we have reported as an inhibitor of the transporter to cells. Moreover, the gene expression is found to be enhanced by hyperosmotic activity and buffering capacity due to polysorbitol and polyethylenimine backbone of PSOAT, respectively. The polysorbitol in PSOAT having polyvalency showed more efficiency in accelerating gene transfer capability than monovalent sorbitol. The above interesting mechanisms display PSOAT as a remarkably potential system to deliver therapeutic (small interfering RNA) and diagnostic agents for effective treatment of cancer. (C) 2011 Elsevier Ltd. All rights reserved.