Targeted microbubbles for ultrasound mediated gene transfection and apoptosis induction in ovarian cancer cells

Ultrasound-targeted microbubble destruction (UTMD) technique can be potentially used for non-viral delivery of gene therapy. Targeting wild-type p53 (wtp53) tumor suppressor gene may provide a clinically promising treatment for patients with ovarian cancer. However, UTMD mediated gene therapy typica...

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Bibliographic Details
Published in:Ultrasonics sonochemistry 2013-01, Vol.20 (1), p.171-179
Main Authors: Chang, Shufang, Guo, Juan, Sun, Jiangchuan, Zhu, Shenyin, Yan, Yu, Zhu, Yi, Li, Min, Wang, Zhigang, Xu, Ronald X.
Format: Article
Language:English
Subjects:
Apoptosis
Cell Line, Tumor
Chemistry
Exact sciences and technology
Female
Gene transfection
General and physical chemistry
Gonadotropin-Releasing Hormone - metabolism
Humans
LHRHa peptide
Microbubbles
Ovarian cancer
Ovarian Neoplasms - pathology
Physical chemistry of induced reactions (with radiations, particles and ultrasonics)
Receptors, LHRH - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Transfection - methods
Tumor Suppressor Protein p53 - genetics
Ultrasonic chemistry
Ultrasonics - methods
Ultrasound
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Summary:Ultrasound-targeted microbubble destruction (UTMD) technique can be potentially used for non-viral delivery of gene therapy. Targeting wild-type p53 (wtp53) tumor suppressor gene may provide a clinically promising treatment for patients with ovarian cancer. However, UTMD mediated gene therapy typically uses non-targeted microbubbles with suboptimal gene transfection efficiency. We synthesized a targeted microbubble agent for UTMD mediated wtp53 gene therapy in ovarian cancer cells. Lipid microbubbles were conjugated with a Luteinizing Hormone–Releasing Hormone analog (LHRHa) via an avidin–biotin linkage to target the ovarian cancer A2780/DDP cells that express LHRH receptors. The microbubbles were mixed with the pEGFP-N1-wtp53 plasmid. Upon exposure to 1MHz pulsed ultrasound beam (0.5W/cm2) for 30s, the wtp53 gene was transfected to the ovarian cancer cells. The transfection efficiency was (43.90±6.19)%. The expression of wtp53 mRNA after transfection was (97.08±12.18)%. The cell apoptosis rate after gene therapy was (39.67±5.95)%. In comparison with the other treatment groups, ultrasound mediation of targeted microbubbles yielded higher transfection efficiency and higher cell apoptosis rate (p
ISSN:1350-4177
1873-2828
DOI:10.1016/j.ultsonch.2012.06.015