title: Ultrasound-Guided Delivery of siRNA and a Chemotherapeutic Drug by Using Microbubble Complexes: In Vitro and In Vivo Evaluations in a Prostate Cancer Model.
abstract: To evaluate the effectiveness of ultrasound and microbubble-liposome complex (MLC)-mediated delivery of siRNA and doxorubicin into prostate cancer cells and its therapeutic capabilities both in vitro and in vivo.
  
  
  
  Microbubble-liposome complexes conjugated with anti-human epidermal growth factor receptor type 2 (Her2) antibodies were developed to target human prostate cancer cell lines PC-3 and LNCaP. Intracellular delivery of MLC was observed by confocal microscopy. We loaded MLC with survivin-targeted small interfering RNA (siRNA) and doxorubicin, and delivered it into prostate cancer cells. The release of these agents was facilitated by ultrasound application. Cell viability was analyzed by MTT assay after the delivery of siRNA and doxorubicin. Survivin-targeted siRNA loaded MLC was delivered into the xenograft mouse tumor model. Western blotting was performed to quantify the expression of survivin in vivo.
  
  
  
  Confocal microscopy demonstrated substantial intracellular uptake of MLCs in LNCaP, which expresses higher levels of Her2 than PC-3. The viability of LNCaP cells was significantly reduced after the delivery of MLCs loaded with siRNA and doxorubicin (85.0 ± 2.9%), which was further potentiated by application of ultrasound (55.0 ± 3.5%, p = 0.009). Survivin expression was suppressed in vivo in LNCaP tumor xenograft model following the ultrasound and MLC-guided delivery of siRNA (77.4 ± 4.90% to 36.7 ± 1.34%, p = 0.027).
  
  
  
  Microbubble-liposome complex can effectively target prostate cancer cells, enabling intracellular delivery of the treatment agents with the use of ultrasound. Ultrasound and MLC-mediated delivery of survivin-targeted siRNA and doxorubicin can induce prostate cell apoptosis and block survivin expression in vitro and in vivo.
authors.affiliation: Department of Radiology, Seoul National University Bundang Hospital, Seongnam 13620, Korea.; Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Bae
authors.affiliation: Department of Radiology, Seoul National University Bundang Hospital, Seongnam 13620, Korea.; Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea.; Program in Nano Science and Technology, Department of Transdisciplinary Studies, Seoul National University Graduate School of Convergence Science and Technology, Suwon 16229, Korea.
authors.forename: Young Il
authors.initials: YI
authors.lastname: Yoon
authors.affiliation: Department of Applied Bioscience, College of Life Science, CHA University, Pocheon 11160, Korea.; College of Pharmacy, Ajou University, Suwon 16499, Korea.
authors.forename: Tae-Jong
authors.initials: TJ
authors.lastname: Yoon
authors.affiliation: Department of Radiology, Seoul National University Bundang Hospital, Seongnam 13620, Korea.; Department of Radiology, Seoul National University College of Medicine, Seoul 03080, Korea.; Program in Nano Science and Technology, Department of Transdisciplinary Studies, Seoul National University Graduate School of Convergence Science and Technology, Suwon 16229, Korea.
authors.forename: Hak Jong
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry; D008297:Male; D051379:Mice; D045423:Microbubbles; D018613:Microscopy, Confocal; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D000077022:Survivin; D014162:Transfection; D014183:Transplantation, Heterologous; D014463:Ultrasonography
chemical_list: D000903:Antibiotics, Antineoplastic; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008081:Liposomes; D034741:RNA, Small Interfering; D000077022:Survivin; D004317:Doxorubicin
keywords: Doxorubicin; Microbubbles; Prostate cancer; Survivin protein, human; siRNA