TY - JOUR
T1 - Microbubble-enhanced ultrasound to deliver an antisense oligodeoxynucleotide targeting the human androgen receptor into prostate tumours
AU - Haag, Petra
AU - Frauscher, Ferdinand
AU - Gradl, Johann
AU - Seitz, Alexander
AU - Schäfer, Georg
AU - Lindner, Jonathan R.
AU - Klibanov, Alexander L.
AU - Bartsch, Georg
AU - Klocker, Helmut
AU - Eder, Iris E.
N1 - Funding Information:
We want to thank Reinhold Ramoner for help with flow cytometry, Hannes Steiner and Andreas P. Berger for their technical assistance with animal experiments. Moreover, we want to thank Radu Rogojanu for his help with TissueQuest software. This work was supported by the Austrian Research Foundation (FWF P16882-B13) and the EU FP6 program (FP6-504587).
PY - 2006/12
Y1 - 2006/12
N2 - 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.
AB - 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.
KW - Androgen receptor
KW - Antisense oligonucleotides
KW - Microbubbles
KW - Prostate cancer
KW - Ultrasound
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U2 - 10.1016/j.jsbmb.2006.09.027
DO - 10.1016/j.jsbmb.2006.09.027
M3 - Article
C2 - 17055720
AN - SCOPUS:33751001045
SN - 0960-0760
VL - 102
SP - 103
EP - 113
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
IS - 1-5 SPEC. ISS.
ER -