title: Ultrasound-targeted microbubble destruction to deliver siRNA cancer therapy.
abstract: Microbubble contrast agents can specifically deliver nucleic acids to target tissues when exposed to ultrasound treatment parameters that mediate microbubble destruction. In this study, we evaluated whether microbubbles and ultrasound-targeted microbubble destruction (UTMD) could be used to enhance delivery of EGF receptor (EGFR)-directed siRNA to murine squamous cell carcinomas. Custom-designed microbubbles efficiently bound siRNA and mediated RNAse protection. UTMD-mediated delivery of microbubbles loaded with EGFR-directed siRNA to murine squamous carcinoma cells in vitro reduced EGFR expression and EGF-dependent growth, relative to delivery of control siRNA. Similarly, serial UTMD-mediated delivery of EGFR siRNA to squamous cell carcinoma in vivo decreased EGFR expression and increased tumor doubling time, relative to controls receiving EGFR siRNA-loaded microbubbles but not ultrasound or control siRNA-loaded microbubbles and UTMD. Taken together, our results offer a preclinical proof-of-concept for customized microbubbles and UTMD to deliver gene-targeted siRNA for cancer therapy.
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Carson
authors.forename: Charles F
authors.initials: CF
authors.lastname: McTiernan
authors.forename: Linda
authors.initials: L
authors.lastname: Lavery
authors.forename: Michelle
authors.initials: M
authors.lastname: Grata
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Leng
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wang
authors.forename: Xucai
authors.initials: X
authors.lastname: Chen
authors.forename: Flordeliza S
authors.initials: FS
authors.lastname: Villanueva
mesh_terms: D000818:Animals; D003287:Contrast Media; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D055785:Gene Knockdown Techniques / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D008809:Mice, Inbred C3H; D045423:Microbubbles; D018307:Neoplasms, Squamous Cell / Q000000981:diagnostic imaging* / Q000235:genetics / Q000628:therapy*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*; D013010:Sonication; D014162:Transfection; D014465:Ultrasonics; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D034741:RNA, Small Interfering; D066246:ErbB Receptors