1. ¹Center for Drug Delivery and Nanomedicine and Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 985830 Nebraska Medical Center, Omaha, NE 68198-5830, USA
2. ²Supratek Pharma, Inc., 215 Boulevard Bouchard, Suite 1315, Laval, Canada, QC H9S1A9

Correspondence: Alexander Kabanov, Center for Drug Delivery and Nanomedicine, Durham Research Center, Room 1036, 985830 Nebraska Medical Center, Omaha, NE 68198-5830, USA. Fax: +1 (402) 559 9365. E-mail: akabanov@unmc.edu

^*Present address: Molecular Diagnostics Laboratory, 985454 Nebraska Medical Center, Omaha, NE 68198-5454, USA.

Received 28 December 2004; Revised 11 July 2005; Accepted 11 July 2005.

Abstract

Amphiphilic block copolymers of poly(ethylene oxide) and poly(propylene oxide) (Pluronics) enhance gene expression, but the mechanism remains unclear. We examined the effects of Pluronics on gene expression in murine cell models (NIH3T3 fibroblasts, C2C12 myoblasts, and Cl66 mammary adenocarcinoma cells) transfected with luciferase and green fluorescent protein. Addition of Pluronics to stably or transiently transfected cells enhanced transcription of the reporter genes. mRNA levels of the heat-shock protein hsp68 were also increased, whereas a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase, was unaffected. Fibroblast and myoblast cells transfected with PathDetect cis-Reporting System constructs were used to examine the involvement of the nuclear factor-B (NF-B) and activating protein-1 (AP-1) in Pluronics enhancement. Pluronics enhanced reporter gene expression controlled by NF-B in both cell models. They also increased expression of a gene under AP-1 in a fibroblast cell line, but not in a myoblast cell line. Activation of the inflammation signaling pathway in myoblast cells by Pluronics was shown by increased IB phosphorylation. No cytotoxicity was observed at doses of Pluronics at which gene expression was increased. Overall, these results indicate that Pluronics can increase the transcription of genes, in part, through the activation of selected stress signaling pathways.