Gene therapy of carcinoma using ultrasound-targeted microbubble destruction.
When microbubble contrast agents are loaded with genes and systemically injected, ultrasound-targeted microbubble destruction (UTMD) facilitates focused delivery of genes to target tissues. A mouse model of squamous cell carcinoma was used to test the hypothesis that UTMD would specifically transduce tumor tissue and slow tumor growth when treated with herpes simplex virus thymidine kinase (TK) and ganciclovir. UTMD-mediated delivery of reporter genes resulted in tumor expression of luciferase and green fluorescent protein (GFP) in perivascular areas and individual tumor cells that exceeded expression in control tumors (p=0.02). The doubling time of TK-treated tumors was longer than GFP-treated tumors (p=0.02), and TK-treated tumors displayed increased apoptosis (p=0.04) and more areas of cellular drop-out (p=0.03). These data indicate that UTMD gene therapy can transduce solid tumors and mediate a therapeutic effect. UTMD is a promising nonviral method for targeting gene therapy that may be useful in a spectrum of tumors.
Center for Ultrasound Molecular Imaging and Therapeutics, Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Andrew R
AR
Carson
Charles F
CF
McTiernan
Linda
L
Lavery
Abigail
A
Hodnick
Michelle
M
Grata
Xiaoping
X
Leng
Jianjun
J
Wang
Xucai
X
Chen
Ruth A
RA
Modzelewski
Flordeliza S
FS
Villanueva
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D008809:Mice, Inbred C3H; D008863:Microspheres; D013010:Sonication; D013937:Thymidine Kinase / Q000235:genetics / Q000627:therapeutic use*; D014162:Transfection / Q000379:methods*; D016896:Treatment Outcome
D013937:Thymidine Kinase
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