Receptor‐mediated delivery of an antisense gene to human brain cancer cells

摘要: Background The goal of this work was the development a gene targeting technology that will enable delivery therapeutic genes to brain cancer cells in vivo following intravenous administration. High-grade gliomas overexpress epidermal growth factor receptor (EGFR) and EGFR antisense therapy could reduce EGFR-dependent gliomas. Methods A human driven by SV40 promoter non-viral plasmid carrying elements facilitate extra-chromosomal replication packaged interior 85 nm pegylated immunoliposomes (PILs). The PILs were targeted U87 glioma with 83-14 murine monoclonal antibody (MAb) insulin (HIR). Results Confocal fluorescent microscopy demonstrated unconjugated HIR MAb is rapidly internalized cells. Endocytosis followed entry into nucleus also for conjugated fluorescein-labeled DNA. delivered exogenous virtually all culture, based on β-galactosidase histochemistry. luciferase resulted levels excess 150 pg/mg protein after 72 h incubation. level expression achieved PIL system comparable lipofectamine. Targeting more than 70% reduction [3H]thymidine incorporation cells; paralleled 79% immunoreactive EGFR. Conclusion The present describes an cells, which results 70–80% inhibition cell growth. provide new approach effective administration without viral vectors. Copyright © 2002 John Wiley & Sons, Ltd.