Microbubble-enhanced ultrasound to deliver an antisense oligodeoxynucleotide targeting the human androgen receptor into prostate tumours
Autor: | Iris E. Eder, Petra Haag, Alexander Seitz, Georg Bartsch, Georg Schäfer, Ferdinand Frauscher, Alexander L. Klibanov, Helmut Klocker, Jonathan R. Lindner, Johann Gradl |
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Rok vydání: | 2006 |
Předmět: |
Male
Pathology medicine.medical_specialty Endocrinology Diabetes and Metabolism Clinical Biochemistry Blotting Western Down-Regulation Mice Nude Biochemistry Oligodeoxyribonucleotides Antisense Prostate cancer Mice Endocrinology Drug Delivery Systems Prostate In vivo medicine Androgen Receptor Antagonists Tumor Cells Cultured Animals Humans Ultrasonics RNA Messenger Molecular Biology Mice Inbred BALB C Microbubbles business.industry Ultrasound Prostatic Neoplasms Cell Biology Transfection Genetic Therapy medicine.disease Xenograft Model Antitumor Assays Androgen receptor Gene Expression Regulation Neoplastic medicine.anatomical_structure Receptors Androgen Cancer research Molecular Medicine business |
Zdroj: | The Journal of steroid biochemistry and molecular biology. 102(1-5) |
ISSN: | 0960-0760 |
Popis: | We have shown recently that downregulation of the androgen receptor (AR), one of the key players in prostate tumor cells, with short antisense oligodeoxynucleotides (ODNs) results in inhibition of prostate tumor growth. Particularly with regard to an application of these antisense drugs in vivo, we now investigated the usefulness of microbubble-enhanced ultrasound to deliver these ODNs into prostate cancer cells. Our short antisense AR ODNs were loaded onto the lipid surface of cationic gas-filled microbubbles by ion charge binding, and delivered into the cells by bursting the loaded microbubbles with ultrasound. In vitro experiments were initially performed to show that this kind of delivery system works in principle. In fact, transfection of prostate tumor cells with antisense AR ODNs using microbubble-enhanced ultrasound resulted in 49% transfected cells, associated with a decrease in AR expression compared to untreated controls. In vivo, uptake of a digoxigenin-labelled ODN was found in prostate tumour xenografts in nude mice following intratumoral or intravenous injection of loaded microbubbles and subsequent exposure of the tumour to ultrasound, respectively. Our results show that ultrasound seems to be the driving force of this delivery system. Uptake of the ODN was also observed in tumors after treatment with ultrasound alone, with only minor differences compared to the combined use of microbubbles and ultrasound. |
Databáze: | OpenAIRE |
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